氨转运体Rhbg和Rhcg在低蛋白饮食大鼠肾脏的表达和调控
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摘要
研究背景
酸碱平衡在很大程度上依赖于氨的代谢。在过去的数年内关于氨代谢产生了许多新的观点。由于机体不断产生内源性和外源性的酸性代谢产物,机体必须产生新的碳酸氢盐以补偿机体碱的消耗,大约60～70%新产生的碳酸氢盐与氨的代谢有关。最近有新的观点认为氨的转运不但依靠非离子化的NH_3扩散,而且依靠特殊转运蛋白实现。
氨产生于近端肾小管,是由谷氨酰胺代谢产生的。在近端肾小管上皮细胞线粒体中,谷氨酰胺在谷氨酰胺酶及谷氨酸脱氢酶的作用下生成氨,一分子谷氨酰胺完全代谢可产生两分子NH_4~+,同时生成两分子碳酸氢钠。上皮细胞产生的碳酸氢钠通过基侧膜进入。肾静脉以补偿机体的碱消耗;产生的氨一部分进入肾小管腔,另一部分进入肾静脉,之后进入肝脏合成尿素。在近端肾小管,氨以NH_4~+的形式分泌入肾小管腔。此处NH_4~+的转运主要依赖上皮细胞顶端膜上的Na~+/H~+交换体NHE-3。近端肾小管产生的氨大部分在髓袢升支粗段被重吸收。由于髓袢升支粗段氨的重吸收作用,到达远端肾小管的氨仅为终尿氨的20%。终尿中的氨80%来自集合管的分泌,集合管氨的转运主要是以NH_3形式通过扩散和转运蛋白介导的方式进行的。新近发现此处介导氨转运的蛋白为Rh(Rhesus)糖蛋白。
Rh糖蛋白包含在由氨运载体AMT(ammonium transporter)、甲氨透明质酸酶MEP(mythylamine permease)和Rh糖蛋白共同构成的与氨转运有关的膜蛋白超家族中。上述蛋白广泛存在于酵母、植物、细菌和许多生物体内,其中AMT主要表达于植物,MEP主要存在于酵母菌,Rh糖蛋白主要表达于动物。研究证明当氮的来源缺乏时,植物根系AMT的转录水平明显增加;外界氮来源的减少诱导酵母菌MEP的表达增加以调控细菌从外界获取氨,证实MEP还可能作为一个缓冲体系以补偿氨的漏出;其他研究提示MEP有氮的感应器的作用。在动物和人类,三个Rh糖蛋白已经被发现并被克隆,他们分别是RhAG/Rhag、RhBG/Rhbg、RhCG/Rhcg。RhAG/Rhag是红系相关性蛋白,RhBG/Rhbg、RhCG/Rhcg是非红系相关性蛋白。有证据显示Rhbg和Rhcg在肾脏氨的代谢和转运中起关键作用。Rh家族蛋白,包括红系相关蛋白Rhag和非红系相关蛋白Rhbg和Rhcg,都发现与AMT和MEP在序列方面有高度的保守性。
低蛋白饮食会造成动物体内氮来源的减少,在低蛋白饮食条件下动物是否能产生与植物和酵母菌相似的变化?Rh糖蛋白是否会在外界蛋白摄入减少的情况下发生变化?以上问题目前尚不清楚,因此本实验通过探讨低蛋白饮食条件下大鼠。肾脏Rhbg和Rhcg表达的变化,从而阐明氨离子通道Rhbg和Rhcg在低蛋白饮食大鼠酸碱调控中的作用,从新的视角探讨肾脏对氨的调控机制,加深对肾脏酸碱调控的认识。
目的观察氨转运蛋白Rhbg和Rhcg对低蛋白饮食大鼠肾脏基因、蛋白质和亚肾单位表达的影响。
方法
1、取低蛋白饮食组和正常对照组大鼠的血清,利用全自动生化分析仪测定血清尿素氮(BUN)、肌酐(Scr)、tCO_2、pH、HCO_3~-、血Na~+、血K~+、血Cl~-。取低蛋白饮食组和正常对照组大鼠的尿液,检测尿氨、尿电解质、尿肌酐,计算电解质清除率(FE_(Na+)、FE_(K+)、FE_(Cl-))。
2、利用western blot分别检测低蛋白饮食组和正常对照组氨转运蛋白Rhbg和Rhcg在大鼠肾脏皮质、内髓、外髓的表达。
3、利用real time-PCR分别检测低蛋白饮食组和正常对照组氨转运蛋白Rhbg和Rhcg基因在大鼠肾脏皮质、内髓、外髓的表达。。
4、利用定量免疫组化的方法检测低蛋白饮食组和正常对照组氨转运蛋白Rhbg和Rhcg在肾小管主细胞和暗细胞表达的变化。
结果
1、在两组大鼠血清中,低蛋白饮食组的BUN明显降低(P＜0.05),血清肌酐、血钾、血钠、血氯在两组间无明显的差别。
2、在两组大鼠尿液中,低蛋白饮食组的尿钠明显降低,尿氨、尿肌酐、尿钾、尿氯两组间无明显的差别。
3、Western blot显示低蛋白饮食可以明显增加Rhbg在大鼠肾脏皮质部的表达(P＜0.05),但不改变Rhbg在内髓和外髓的表达。Rhcg在两组大鼠肾脏的皮质部、内髓和外髓的表达无明显变化。
4、Real Time PCR显示两组大鼠肾脏的皮质部、内髓和外髓部Rhbg和Rhcg mRNA表达无明显差别。
5、定量免疫组化染色技术提示在低蛋白饮食组大鼠肾脏皮质集合管的主细胞和暗细胞中,Rhbg的表达明显增强(P＜0.05);内髓集合管和外髓集合管的主细胞和暗细胞Rhbg的表达无明显改变。
6、免疫组化染色技术提示Rhcg在两组大鼠肾脏的皮质部、内髓和外髓的表达无明显变化。
结论低蛋白饮食增加Rhbg在大鼠肾脏皮质集合管主细胞和暗细胞的表达,该作用独立于mRNA水平的变化。在低蛋白饮食大鼠肾脏调控中,Rhcg介导的氨转运可能不起作用。
Background Acid-base homeostasis depends on renal ammonia metabolism.The generation of new bicarbonate is necessary to replace the alkali consumed in the buffering of endogenous and exogenous acids.Under normal conditions 60-70%of the new bicarbonate formed by the kidney is due to renal ammonia metabolism. Recent studies have yielded important new insights into the mechanisms of renal ammonia transport.In particular,the theory that ammonia transport occurs almost exclusively through nonionic NH_3 diffusion has been replaced by the observation that a variety of proteins specifically transport NH_3 and NH_4~+ and that this transport is critical for normal ammonia metabolism.
Renal ammonia metabolism and transport involve integrated responses of multiple portions of the kidney,including specific transport mechanisms in the proximal tubule, thick ascending limb of the loop of Henle,and the collecting duct.Proximal tubule segments metabolize the amino acid,glutamine,producing equal amounts of NH_4~+ and bicarbonate molecules.The proximal tubule secretes NH_4~+ into the luminal fluid primarily through the action of the apical sodium/hydrogen ion exchanger,NHE-3.In the thick ascending limb of the loop of Henle,the apical Na~+-K~-/2Cl~- cotransporter NKCC2 predominantly reabsorbs the majority of luminal ammonia into the renal interstitium that result in renal interstitial ammonia accumulation.And then,the collecting duct secrets ammonia of the renal interstitium into the luminal fluid. Approximately,70-80%of total urinary ammonia is secreted by the collecting duct, indicating the important role of understanding the metabolism of collecting duct ammonia transport.
An important evidence suggests ammonium transporter(Amt)/ mythylamine permease(MEP)/human Rhesus(Rh) glycoprotein protein family functions as vital role in ammonia metabolism and transport.Plant,bacterial Amt and MEP are subject to the nitrogen control and the expression is increased under poor nitrogen supply. Furthermore,MEP may function both to ammonia transport and to component of nitrogen sensor.In human,the Rh family of protein,both erythroid(Rhag) and nonerythroid(Rhbg and Rhcg),also show conservation with the Amt and MEP family throughout their consequence.We hypothesis that it might have the similar regulation in the condition of low protein diet in animal;and then to illuminate the Rh glycoprotein's role in the low protein diet;to explore the mechanism of ammonia regulation in the kidney;to deepen the recognition to the regulation of Acid-base of kidney.
Objective To explore the effect of the ammonia transporters,Rhbg and Rhcg,in response to low protein diet.
Methods
1.To explore the BUN,Creatinine,K~+,Na~+,Cl~- of the serum between low protein diet and control;to explore the ammonia、Creatinine,K~+,Na~+,Cl~- of the urine between low protein diet and control.
2.Detect the protein expression of Rhbg and Rhcg in cortex,outer medullar,inner medulla between low protein diet and normal control by Western blot.
3.Detect the mRNA expression of Rhbg and Rhcg in cortex,outer medullar,inner medulla between low protein diet and control by real-time PCR
4.Using single labeling,double labling and quantitative immunohistochemistry to detect the expression of Rhbg and Rhcg in principal cells and intercalated cells in CCD,OMCD,IMCD.
Results
1.Physiological'date.
Serum:Rats fed with low protein diet showed significantly lower in BUN(19.7±3.9 VS 13.3±1.5 mg/dl) and CO2(25.2±1.3 VS 22.9±2.2 mmol/L) values,but not difference in Creatinine,K~+,Na~+,Cl~-.
Urine:Rats fed with low protein diet showed significantly lower in Na~+ (192.83±2408.97 VS 45±1319.6),FE_(Na+)(0.80±0.06 VS 0.18±0.03) and had no difference in urea,creatinine,K~+,Na~+,Cl~-,FE_(K+),FE_(Cl-),and FE_(Urea).
2.Rhbg protein expression:Low protein diet significantly increased Rhbg in high molecular weigh(trimeric) expression and no change in outer medulla,inner medulla (P＜0.05,n = 6 in each group).
3.Rhcg protein expression:No difference in Rhcg immunoreactivity was observed in proteins isolated from the cortex,outer medulla,or inner medulla.
4.Rhbg mRNA quantification:We next quantified Rhbg mRNA expressions.No significant differences in Rhbg mRNA expression was observed in any of these regions.
5.Rhcg mRNA quantification:We quantified Rhcg mRNA expressions.No significant differences in Rhcg mRNA expression was observed in any of these regions.
6.Rhbg immunolocalization:In the cortex of the kidney from low protein diet rats, more intensity of immunolabel was observed than from control,but no difference was demonstrated between outer medulla and inner medulla.
7.Rhcg immunolocalization.In kidneys from low protein diet rat,there were no detectable differences in Rhcg immunoreactivity in the cortex,outer medulla,or the inner medulla.
8.Morphometric and quantitative immunohistochemistry analysis.The Rhbg immunoreactivity increased significantly between low protein diet and control both in the principal cells and intercalated cells of cortical collecting duct.
Conclusion Low protein diet increases Rhbg expression in the cortex,especially in trimeric state and this increase is consistence with more distinct difference in basolateral Rhbg immunoreactivity especially in the principal cells and intercalated cells in CCD.It is possible that Rhcg-mediated ammonia transport is not regulated in response to low protein diet.
酸碱平衡在很大程度上依赖于氨的代谢。在过去的数年内关于氨代谢产生了许多新的观点。由于机体不断产生内源性和外源性的酸性代谢产物,机体必须产生新的碳酸氢盐以补偿机体碱的消耗,大约60～70%新产生的碳酸氢盐与氨的代谢有关。最近有新的观点认为氨的转运不但依靠非离子化的NH_3扩散,而且依靠特殊转运蛋白实现。
氨产生于近端肾小管,是由谷氨酰胺代谢产生的。在近端肾小管上皮细胞线粒体中,谷氨酰胺在谷氨酰胺酶及谷氨酸脱氢酶的作用下生成氨,一分子谷氨酰胺完全代谢可产生两分子NH_4~+,同时生成两分子碳酸氢钠。上皮细胞产生的碳酸氢钠通过基侧膜进入。肾静脉以补偿机体的碱消耗;产生的氨一部分进入肾小管腔,另一部分进入肾静脉,之后进入肝脏合成尿素。在近端肾小管,氨以NH_4~+的形式分泌入肾小管腔。此处NH_4~+的转运主要依赖上皮细胞顶端膜上的Na~+/H~+交换体NHE-3。近端肾小管产生的氨大部分在髓袢升支粗段被重吸收。由于髓袢升支粗段氨的重吸收作用,到达远端肾小管的氨仅为终尿氨的20%。终尿中的氨80%来自集合管的分泌,集合管氨的转运主要是以NH_3形式通过扩散和转运蛋白介导的方式进行的。新近发现此处介导氨转运的蛋白为Rh(Rhesus)糖蛋白。
Rh糖蛋白包含在由氨运载体AMT(ammonium transporter)、甲氨透明质酸酶MEP(mythylamine permease)和Rh糖蛋白共同构成的与氨转运有关的膜蛋白超家族中。上述蛋白广泛存在于酵母、植物、细菌和许多生物体内,其中AMT主要表达于植物,MEP主要存在于酵母菌,Rh糖蛋白主要表达于动物。研究证明当氮的来源缺乏时,植物根系AMT的转录水平明显增加;外界氮来源的减少诱导酵母菌MEP的表达增加以调控细菌从外界获取氨,证实MEP还可能作为一个缓冲体系以补偿氨的漏出;其他研究提示MEP有氮的感应器的作用。在动物和人类,三个Rh糖蛋白已经被发现并被克隆,他们分别是RhAG/Rhag、RhBG/Rhbg、RhCG/Rhcg。RhAG/Rhag是红系相关性蛋白,RhBG/Rhbg、RhCG/Rhcg是非红系相关性蛋白。有证据显示Rhbg和Rhcg在肾脏氨的代谢和转运中起关键作用。Rh家族蛋白,包括红系相关蛋白Rhag和非红系相关蛋白Rhbg和Rhcg,都发现与AMT和MEP在序列方面有高度的保守性。
低蛋白饮食会造成动物体内氮来源的减少,在低蛋白饮食条件下动物是否能产生与植物和酵母菌相似的变化?Rh糖蛋白是否会在外界蛋白摄入减少的情况下发生变化?以上问题目前尚不清楚,因此本实验通过探讨低蛋白饮食条件下大鼠。肾脏Rhbg和Rhcg表达的变化,从而阐明氨离子通道Rhbg和Rhcg在低蛋白饮食大鼠酸碱调控中的作用,从新的视角探讨肾脏对氨的调控机制,加深对肾脏酸碱调控的认识。
目的观察氨转运蛋白Rhbg和Rhcg对低蛋白饮食大鼠肾脏基因、蛋白质和亚肾单位表达的影响。
方法
1、取低蛋白饮食组和正常对照组大鼠的血清,利用全自动生化分析仪测定血清尿素氮(BUN)、肌酐(Scr)、tCO_2、pH、HCO_3~-、血Na~+、血K~+、血Cl~-。取低蛋白饮食组和正常对照组大鼠的尿液,检测尿氨、尿电解质、尿肌酐,计算电解质清除率(FE_(Na+)、FE_(K+)、FE_(Cl-))。
2、利用western blot分别检测低蛋白饮食组和正常对照组氨转运蛋白Rhbg和Rhcg在大鼠肾脏皮质、内髓、外髓的表达。
3、利用real time-PCR分别检测低蛋白饮食组和正常对照组氨转运蛋白Rhbg和Rhcg基因在大鼠肾脏皮质、内髓、外髓的表达。。
4、利用定量免疫组化的方法检测低蛋白饮食组和正常对照组氨转运蛋白Rhbg和Rhcg在肾小管主细胞和暗细胞表达的变化。
结果
1、在两组大鼠血清中,低蛋白饮食组的BUN明显降低(P＜0.05),血清肌酐、血钾、血钠、血氯在两组间无明显的差别。
2、在两组大鼠尿液中,低蛋白饮食组的尿钠明显降低,尿氨、尿肌酐、尿钾、尿氯两组间无明显的差别。
3、Western blot显示低蛋白饮食可以明显增加Rhbg在大鼠肾脏皮质部的表达(P＜0.05),但不改变Rhbg在内髓和外髓的表达。Rhcg在两组大鼠肾脏的皮质部、内髓和外髓的表达无明显变化。
4、Real Time PCR显示两组大鼠肾脏的皮质部、内髓和外髓部Rhbg和Rhcg mRNA表达无明显差别。
5、定量免疫组化染色技术提示在低蛋白饮食组大鼠肾脏皮质集合管的主细胞和暗细胞中,Rhbg的表达明显增强(P＜0.05);内髓集合管和外髓集合管的主细胞和暗细胞Rhbg的表达无明显改变。
6、免疫组化染色技术提示Rhcg在两组大鼠肾脏的皮质部、内髓和外髓的表达无明显变化。
结论低蛋白饮食增加Rhbg在大鼠肾脏皮质集合管主细胞和暗细胞的表达,该作用独立于mRNA水平的变化。在低蛋白饮食大鼠肾脏调控中,Rhcg介导的氨转运可能不起作用。
Background Acid-base homeostasis depends on renal ammonia metabolism.The generation of new bicarbonate is necessary to replace the alkali consumed in the buffering of endogenous and exogenous acids.Under normal conditions 60-70%of the new bicarbonate formed by the kidney is due to renal ammonia metabolism. Recent studies have yielded important new insights into the mechanisms of renal ammonia transport.In particular,the theory that ammonia transport occurs almost exclusively through nonionic NH_3 diffusion has been replaced by the observation that a variety of proteins specifically transport NH_3 and NH_4~+ and that this transport is critical for normal ammonia metabolism.
Renal ammonia metabolism and transport involve integrated responses of multiple portions of the kidney,including specific transport mechanisms in the proximal tubule, thick ascending limb of the loop of Henle,and the collecting duct.Proximal tubule segments metabolize the amino acid,glutamine,producing equal amounts of NH_4~+ and bicarbonate molecules.The proximal tubule secretes NH_4~+ into the luminal fluid primarily through the action of the apical sodium/hydrogen ion exchanger,NHE-3.In the thick ascending limb of the loop of Henle,the apical Na~+-K~-/2Cl~- cotransporter NKCC2 predominantly reabsorbs the majority of luminal ammonia into the renal interstitium that result in renal interstitial ammonia accumulation.And then,the collecting duct secrets ammonia of the renal interstitium into the luminal fluid. Approximately,70-80%of total urinary ammonia is secreted by the collecting duct, indicating the important role of understanding the metabolism of collecting duct ammonia transport.
An important evidence suggests ammonium transporter(Amt)/ mythylamine permease(MEP)/human Rhesus(Rh) glycoprotein protein family functions as vital role in ammonia metabolism and transport.Plant,bacterial Amt and MEP are subject to the nitrogen control and the expression is increased under poor nitrogen supply. Furthermore,MEP may function both to ammonia transport and to component of nitrogen sensor.In human,the Rh family of protein,both erythroid(Rhag) and nonerythroid(Rhbg and Rhcg),also show conservation with the Amt and MEP family throughout their consequence.We hypothesis that it might have the similar regulation in the condition of low protein diet in animal;and then to illuminate the Rh glycoprotein's role in the low protein diet;to explore the mechanism of ammonia regulation in the kidney;to deepen the recognition to the regulation of Acid-base of kidney.
Objective To explore the effect of the ammonia transporters,Rhbg and Rhcg,in response to low protein diet.
Methods
1.To explore the BUN,Creatinine,K~+,Na~+,Cl~- of the serum between low protein diet and control;to explore the ammonia、Creatinine,K~+,Na~+,Cl~- of the urine between low protein diet and control.
2.Detect the protein expression of Rhbg and Rhcg in cortex,outer medullar,inner medulla between low protein diet and normal control by Western blot.
3.Detect the mRNA expression of Rhbg and Rhcg in cortex,outer medullar,inner medulla between low protein diet and control by real-time PCR
4.Using single labeling,double labling and quantitative immunohistochemistry to detect the expression of Rhbg and Rhcg in principal cells and intercalated cells in CCD,OMCD,IMCD.
Results
1.Physiological'date.
Serum:Rats fed with low protein diet showed significantly lower in BUN(19.7±3.9 VS 13.3±1.5 mg/dl) and CO2(25.2±1.3 VS 22.9±2.2 mmol/L) values,but not difference in Creatinine,K~+,Na~+,Cl~-.
Urine:Rats fed with low protein diet showed significantly lower in Na~+ (192.83±2408.97 VS 45±1319.6),FE_(Na+)(0.80±0.06 VS 0.18±0.03) and had no difference in urea,creatinine,K~+,Na~+,Cl~-,FE_(K+),FE_(Cl-),and FE_(Urea).
2.Rhbg protein expression:Low protein diet significantly increased Rhbg in high molecular weigh(trimeric) expression and no change in outer medulla,inner medulla (P＜0.05,n = 6 in each group).
3.Rhcg protein expression:No difference in Rhcg immunoreactivity was observed in proteins isolated from the cortex,outer medulla,or inner medulla.
4.Rhbg mRNA quantification:We next quantified Rhbg mRNA expressions.No significant differences in Rhbg mRNA expression was observed in any of these regions.
5.Rhcg mRNA quantification:We quantified Rhcg mRNA expressions.No significant differences in Rhcg mRNA expression was observed in any of these regions.
6.Rhbg immunolocalization:In the cortex of the kidney from low protein diet rats, more intensity of immunolabel was observed than from control,but no difference was demonstrated between outer medulla and inner medulla.
7.Rhcg immunolocalization.In kidneys from low protein diet rat,there were no detectable differences in Rhcg immunoreactivity in the cortex,outer medulla,or the inner medulla.
8.Morphometric and quantitative immunohistochemistry analysis.The Rhbg immunoreactivity increased significantly between low protein diet and control both in the principal cells and intercalated cells of cortical collecting duct.
Conclusion Low protein diet increases Rhbg expression in the cortex,especially in trimeric state and this increase is consistence with more distinct difference in basolateral Rhbg immunoreactivity especially in the principal cells and intercalated cells in CCD.It is possible that Rhcg-mediated ammonia transport is not regulated in response to low protein diet.
引文
[1] DuBose TD Jr, Good DW, Hamm LL, et al. Ammonium transport in the kidney, new physiological concepts and their clinical implications. J. Am. Soc. Nephron, 1991,1:1193-203.
[2] Weiner, I David. The Rh gene family and renal ammonium transport. Curr Opin Nephrol Hypertens. 2004,13(5), 533-540.
[3] I. David Weiner, L. Lee Hamm. Molecular Mechanisms of Renal Ammonia Transport. Annual Review of Physiology.2007, 69: 317-340.
[4] Hamm LL, Simon EE. Roles and mechanisms of urinary buffer excretion. Am. J. Physiol.Renal Physiol. 1987, 253:F595-605.
[5] Sajo IM, Goldstein MB, Sonnenberg H, et al. Sites of ammonia addition to tubular fluid in rats with chronic metabolic acidosis. Kidney Int. 1982, 20:353-58.
[6] Knepper MA. NH_4~+ transport in the kidney. Kidney Int.1991,40: S95-S102.
[7] Tannen RL, Sahai A. Biochemical pathways and modulators of renal ammoniagenesis.Miner Electrolyte Metab, 1990,16:249-258.
[8] Nagami GT. Ammonia production and secretion by the proximal tubule. Am J Kidney Dis.1989,14:258-261.
[9] Simon EE, Merli C, Herndon J, et al. Effects of barium and 5-(N-ethyl-N-isopropyl)-amiloride on proximal tubule ammonia transport. Am J Physiol. 1992,262:F36-F39.
[10] Hamm LL, Simon EE. Ammonia transport in the proximal tubule. Min Electrolyte Metab.1990,16:283-290.
[11] Kikeri D, Sun A, Zeidel ML, et al. Cell membranes impermeable to NH3.Nature. 1989,339:478-480.
[12] Amlal H, Paillard M, Bichara M. NH4+ transport pathways in cells of medullary thick ascending limb of rat kidney. NH4+ conductance and K+/NH4+(H+) antiport. J Biol Chemistry. 1994,269:21962-21971.
[13] Attmane-Elakeb A, Amlal H, Bichara M. Ammonium carriers in medullary thick ascending limb. Am J Physiol Renal Physiol. 2001, 280:F1-F9.
[14] Bettinelli A, Ciarmatori S, Cesareo L, et al. Phenotypic variability in Bartter syndrome type I. Pediatric Nephrol, 2000,14:940-945.
[15] Rodriguez-Soriano J. Bartter and related syndromes: the puzzle is almost solved.Pediatric Nephrol .1998,12:315-327.
[16] Melton LB, Vanatta JC. Ammonia transport by the urinary bladder of Bufo marinus.Comp Biochem Physiol A Physiol. 1996,115:153-158.
[17] Wall SM. NH4+ augments net acid-secretion by a ouabain-sensitive mechanism in isolated-perfused inner medullary collecting ducts. Am J Physiol. 1996, 270:F432-F439.
[18] Dubois E, Grenson M. Methylamine/ammonia uptake systems in Saccharomyces cerevisiae: multiplicity and regulation. Mol Gen Genet. 1979,175:67-76.
[19] Marini AM, Vissers S, Urrestarazu A, et al. Cloning and expression of the MEP1 gene encoding an ammonium transporter in Saccharomyces cerevisiae. EMBO J.1994, 13:3456-3463.
[20] Ninnemann O, Jauniaux JC, Frommer WB. Identification of a high affinity NH4+ transporter from plants. EMBO J.1994, 13:3464-3471.
[21] Marini AM, Soussi-Boudekou S, Vissers S, et al. A family of ammonium transporters in Saccharomyces cerevisiae. Mol Cell Biol.1997; 17:4282-4293.
[22] von Wiren N, Gazzarrini S, Gojon A, et al. The molecular physiology of ammonium uptake and retrieval. Curr Opin Plant Biol. 2000; 3:254-261.
[23] Marini AM, Urrestarazu A, Beauwens R, et al. The Rh (rhesus) blood group polypeptides are related to NH4+ transporters. Trends Biochem Sci.1997, 22:460-461.
[24] Liu Z, Peng J, Mo R, Hui CC, et al. Rh type B glycoprotein is a new member of the Rh superfamily and a putative ammonia transporter in mammals. J Biol Chem.2001, 276: 1424-1433.
[25] Liu Z, Chen Y, Mo R, et al. Characterization of human RhCG and mouse Rhcg as novel nonerythroid Rh glycoprotein homologues predominantly expressed in kidney and testis. J Biol Chem. 2000, 275: 25641-25651.
[26] Ludewig U. Electroneutral ammonium transport by basolateral Rhesus B glycoprotein. J Physiol. 2004, 559: 751-759.
[27] Mak DD, Dang B, Weiner ID, et al. Characterization of transport by the kidney Rh glycoproteins, RhBG and RhCG. Am J Physiol Renal Physiol .2006, 290(2):F297-305.
[28] Nakhoul NL, DeJong H, Abdulnour-Nakhoul SM, et al. Characteristics of renal Rhbg as an NH_4~+ transporter. Am J Physiol Renal Physiol .2005, 288: F170-F181.
[29] Planelles G. Ammonium homeostasis and human Rhesus glycoproteins. Nephron Physio.2007, 105:11-7,2007
[30] Handlogten ME, Hong SP, Zhang L, et al. Expression of the ammonia transporter proteins, Rh B glycoprotein and Rh C glycoprotein, in the intestinal tract. Am J Physiol Gastrointest Liver Physiol.2005, 288 : G1036 -G1047.
[31] Verlander JW, Miller RT, Frank AE, et al. Localization of the ammonium transporter proteins, RhBG and RhCG, in mouse kidney. Am J Physiol Renal Physiol.2003, 284: F323-F337.
[32] Eladari D, Cheval L, Quentin F, et al. Expression of RhCG, a new putative NH(3)/NH(4)(+) transporter, along the rat nephron. J Am Soc Nephrol. 2002,13:1999-2008
[33] Nielsen S, Fr(?)ki?r J, Marples D, et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev.2002, 82(1):205-44.
[34] Handlogten ME, Hong SP, Zhang L, et al. Expression of the ammonia transporter proteins, Rh B glycoprotein and Rh C glycoprotein, in the intestinal tract. Am J Physiol Gastrointest Liver Physiol. 2005, 288 : G1036 -G1047.
[35] Weiner ID, Miller RT, and Verlander JW. Localization of the ammonium transporters,Rh B glycoprotein and Rh C glycoprotein in the mouse liver. Gastroenterology. 2003, 124:1432-1440.
[36] Weiner ID.Expression of the non-erythroid Rh glycoproteins in mammalian tissues. Transfus Clin Biol. 2006,13:159-63.
[37] Han KH, Croker BP, Clapp WL, et al. Expression of the ammonia transporter, Rh C glycoprotein, in normal and neoplastic human kidney. J. Am. Soc. Nephrol. 2006,17(10):2670-2679.
[38] Seshadri RM, Klein JD, Kozlowski S, et al. Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis. Am J Physiol Renal Physiol. 2006, 290 : F397 -F408.
[39] Gazzarrini S, Lejay L, Gojon A, et al. Three functional transporters for constitutive,diumally regulated, and starvation-induced uptake of ammonium into Arabidopsis roots. Plant Cell. 1999, 11:937-48.
[40] Lorenz MC, Heitman J. The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO J.1998,17:1236-1247.
[1] Isozaki T, Verlander JW, and Sands JM. Low protein diet alters urea transport and cell structure in rat initial inner medullary collecting duct. J. Clin. Invest 1993, 92: 2448-2457.
[2] Isozaki T, Gillin AG, Swanson CE, et al. Protein restriction sequentially induces new urea transport processes in rat initial IMCDs. Am.J. Physiol.1994,266:F756-F761.
[3] Peil AE, Stolte H, and Schmidt-Nielsen B. Uncoupling of glomerular and tubular regulations of urea excretion in rat. Am. J. Physiol. 1990, 258: F1666-F1674.
[4] Klein JD, Sands JM, Qian L, et al. Upregulation of urea transporter UT-A2 and water channels AQP2 and AQP3 in mice lacking urea transporter UT-B. J Am Soc Nephrol.2004,15:1161-1167.
[5] Handlogten ME, Hong SP, Westhoff CM, et al. Basolateral ammonium transport by the mouse inner medullary collecting duct cell (mIMCD-3). Am J Physiol Renal Physiol.2004,287:F628-F638.
[6] Verlander JW, Miller RT, Frank AE, et al. Localization of the ammonium transporter proteins, RhBG and RhCG, in mouse kidney. Am J Physiol Renal Physiol. 2003, 284: F323-F337.
[7] Weiner ID, Miller RT, and Verlander JW. Localization of the ammonium transporters, Rh B glycoprotein and Rh C glycoprotein in the mouse liver. Gastroenterology. 2003,124: 1432-1440.
[8] Handlogten ME, Hong SP, Westhoff CM, et al. Apical ammonia transport by the mouse inner medullary collecting duct, mIMCD-3, cell. Am J Physiol Renal Physiol.2005, 289:F347-F358.
[9] Handlogten ME, Hong SP, Zhang L, et al. Expression of the ammonia transporter proteins,Rh B glycoprotein and Rh C glycoprotein, in the intestinal tract. Am J Physiol Gastrointest Liver Physiol. 2005,288 : G1036 -G1047.
[10] Seshadri RM, Klein JD, Kozlowski S, et al. Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis. Am J Physiol Renal Physiol.2006, 290 : F397 -F408.
[11] Quentin F, Eladari D, Cheval L, et al. RhBG and RhCG, the putative ammonia transporters, are expressed in the same cells in the distal nephron. J Am Soc Nephrol.2003, 14:545-554.
[12] Eladari D, Cheval L, Quentin F, et al. Expression of RhCG, a new putative NH(3)/NH(4)(+) transporter, along the rat nephron. J Am Soc Nephrol.2002,13:1999-2008.
[13] Marini AM, Urrestarazu A, Beauwens R, et al. The Rh (rhesus) blood group polypeptides are related to NH4+ transporters. Trends Biochem Sci. 1997, 22:460-461.
[14] Marini AM, Matassi G, Raynal V, et al. The human rhesus-associated RhAG protein and a kidney homologue promote ammonium transport in yeast. Nat Genet 2000,26:341-344.
[15] Liu Z, Chen Y, Mo R, et al. Characterization of human RhCG and mouse Rhcg as novel nonerythroid Rh glycoprotein homologues predominantly expressed in kidney and testis. J Biol Chem.2000, 27-5:25641-25651.
[16] Liu Z, Peng J, Mo R, et al. Rh type B glycoprotein is a new member of the Rh superfamily and a putative ammonia transporter in mammals. J Biol Chem.2001, 276:1424-1433.
[17] I. David Weiner, L. Lee Hamm. Molecular Mechanisms of Renal. Ammonia Transport.Annual Review of Physiology.2007, 69: 317-340.
[18] Lopez C, Metral S, Eladari D, Drevensek S, Gane P, et al. The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells. J. Biol. Chem. 2004, 280:8221-28
[19] Chambrey R, Goossens D, Bourgeois S, et al . Genetic ablation of Rhbg in mouse does not impair renal ammonium excretion. Am. J. Physiol Renal Physiol. 2005, 289:F1281-F1290.
[20] Kim YH, Verlander JW, Matthews SW, et al, Everett LA, Green ED, Nielsen S, Wall SM. Intercalated cell H~+/OH~- transporter expression is reduced in Slc26a4 null mice. Am. J.Physiol. Renal Physiol .2005, 289:F1262-72.
[21] Gazzarrini S, Lejay L, Gojon A, et al. Three functional transporters for constitutive, diurnally regulated, and starvation-induced uptake of ammonium into Arabidopsis roots. Plant Cell. 1999, 11:937-48.
[22] von Wiren N, Gazzarrini S, Gojon A, et al et al. The molecular physiology of ammonium uptake and retrieval. Curr Opin Plant Biol. 2000, 3:254-61.
[23] Marini AM, Soussi-Boudekou S, Vissers S, et al. A family of ammonium transporters in Saccharomyces cerevisiae. Mol Cell Biol. 1997,17:4282-4293.
[24] Peng J and Huang CH. Rh proteins vs Amt proteins: an organismal and phylogenetic perspective on CO_2 and NH_3 gas channels. Transfus Clin Biol.2006,13:85-94.
[25] Mak DD, Dang B, Weiner ID, et al. 2006. Characterization of transport by the kidney Rh glycoproteins, RhBG and RhCG. Am. J. Physiol. Renal Physiol. 290:F297-305.
[26] Ludewig U. 2004. Electroneutral ammonium transport by basolateral Rhesus B glycoprotein. J. Physiol. 559:751-59.
[27] Zidi-Yahiaoui N, Mouro-Chanteloup I, D'Ambrosio AM, et al. Human Rhesus B and Rhesus C glycoproteins: properties of facilitated ammonium transport in recombinant kidney cells. Biochem. J.2005, 391:33-40.
[28] Palkova Z, Janderova B., Gabriel J, et al. Ammonia mediates communication between yeast colonies. Nature. 1997, 390:532-536.
[29] Lorenz MC, and Heitman J. The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO J. 1998, 17,1236-1247.
[30] Johansson FK, Brodd J, Eklof C, et al. Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging. Proc Natl Acad Sci USA.2004,101: 11334-11337.
[31] Conroy MJ, Jamieson SJ, Blakey D, et al. Electron and atomic force microscopy of the trimeric ammonium transporter AmtB. EMBO Rep. 2004, 5:1153-1158.
[32] Khademi S, O'Connell J Ⅲ, Remis J, et al. Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 (?). Science.2004, 305:1587-1594.
[33] Zheng L, Kostrewa D, Berneche S, et al. The mechanism of ammonia transport based on the crystal structure of AmtB of Escherichia coli. Proc Natl. Acad Sci .2004,101:17090-95.
[34] Marini AM, Boeckstaens M, Benjelloun F. et al. Structural involvement in substrate recognition of an essential aspartate residue conserved in Mep/Amt and Rh-type ammonium transporters. Curr Genet.2006, 49(6):364-74.
[35] Conroy MJ, Jamieson SJ, Blakey D, et al, Merrick M, Bullough PA. Electron and atomic force microscopy of the trimeric ammonium transporter AmtB. EMBO Rep. 5:1153-1158,2004.
[36] Bastani B, Haragsim L. Immunocytochemistry of renal H-ATPase. Miner Electrolyte Metab.1996, 22(5-6):382-95.
[37] Nielsen S, DiGiovanni SR, Christensen EI, et al. Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci USA. 1993, 90: 11663-11667.
[38] Nielsen S, Fr(?)ki?r J, Marples D, et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002, 82(1):205-44.
[39] Han KH, Croker BP, Clapp WL, et al. Expression of the ammonia transporter, Rh C glycoprotein, in normal and neoplastic human kidney. J. Am. Soc. Nephrol.2006,17(10):2670-2679.
[40] Marples D, Knepper MA, Christensen EI, et al. Redistribution of aquaporin-2 water channels induced by vasopressin in rat kidney inner medullary collecting duct. Am J Physiol Cell Physiol. 269: C655-C664,1995.
[41] Lopez C, Métral S, Eladari, et al. The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells. J Biol Chem.2005, 280:8221-8228.
[42] Star RA, Kurtz I, Mejia R, et al. Disequilibrium pH and ammonia transport in isolated perfused cortical collecting ducts. Am. J. Physiol(Renal Fluid Electrolyte Physiol ).1987,253:F1232-F1242.
[42] Yip KP and Kurtz I. NH_3 permeability of principal cells and intercalated cells measured by confocal fluorescence imaging. Am J Physiol Renal Fluid Electrolyte Physiol. 1995, 269:F545-F550.
[43] Planelles G. Ammonium homeostasis and human Rhesus glycoproteins. Nephron Physiol.2007, 105:11-7.
[44] Weiner ID.Expression of the non-erythroid Rh glycoproteins in mammalian tissues.Transfus. Clin. Biol. 2006,13:159-63.
[45] Seshadri RM, Klein JD, Smith T, et al. Changes in the subcellular distribution of the ammonia transporter Rhcg, in response to chronic metabolic acidosis. Am. J. Physiol. Renal Physiol. 2006, 290:F1443-52.
[46] Bakouh N, Benjelloun F, Hulin P, et al. NH_3 is involved in the NH_4~+ transport induced by the functional expression of the human Rh C glycoprotein. J. Biol. Chem. 2004,279:15975-83.
[47] Nakhoul NL, Palmer SA, Abdulnour-Nakhoul S, et al. Ammonium transport in oocytes expressing Rheg. FASEB J.2002, 16(4):A53 (Abstr.)
[48] Weiner ID.The Rh gene family and renal ammonium transport. Curr. Opin. Nephrol.Hypertens. 2004,13:533-40.
[49] Bakouh N, Benjelloun F, Hulin P, et al et al. NH_3 is involved in the NH_4~+ transport induced by the functional expression of the human Rh C glycoprotein. J Biol Chem.2004, 279:15975-15983.
[1] Haussinger D, Lamers WH, Moorman AF. Hepatocyte heterogeneity in the metabolism of amino acids and ammonia. Enzyme. 1992, 46:72-93.
[2] Kikeri D, Sun A, Zeidel ML, Hebert SC. Cell membranes impermeable to NH_3. Nature. 1989,339:478-80.
[3] Amlal H, Paillard M, Bichara M.NH_4~+ transport pathways in cells of medullary thick ascending limb of rat kidney. NH_4~+ conductance and K~+/NH_4~+ (H~+) antiport. J. Biol. Chem. 1994, 269:21962-71.
[4] Attmane-Elakeb A, Amlal H, Bichara M. Ammonium carriers in medullary thick ascending limb. Am. J. Physiol. Renal Physiol.2001, 280:F1-9.
[5] Flessner MF, Mejia R, Knepper MA. Ammonium and bicarbonate transport in isolated perfused rodent long-loop thin descending limbs. Am. J. Physiol. 1993, 264:F388-96. [6] Mejia R, Flessner MF, Knepper MA. Model of ammonium and bicarbonate transport along LDL: implications for alkalinization of luminal fluid. Am. J. Physiol. Renal Physiol. 1993, 264:F397-403.
[7] DuBose TD Jr, Good DW, Hamm LL, Wall SM. Ammonium transport in the kidney: new physiological concepts and their clinical implications. J. Am. Soc. Nephrol. 1991,1:1193-203 [8] Hamm LL, Simon EE. Roles and mechanisms of urinary buffer excretion. Am. J. Physiol. Renal Physiol. 1987, 253:F595-605.
[9] Handlogten ME, Hong SP, Westhoff CM, Weiner ID.Basolateral ammonium transport by the mouse inner medullary collecting duct cell (mIMCD-3). Am. J. Physiol. Renal Physiol.2004, 287:F628-38.
[10] Handlogten ME, Hong SP, Westhoff CM, Weiner ID. Apical ammonia transport by the mouse inner medullary collecting duct cell (mIMCD-3).Am J Physiol Renal Physiol.2005,289(2):F347-58.
[11] Khademi S, O'Connell J Ⅲ, Remis J, Robles-Colmenares Y, Miercke LJ, Stroud RM. Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 A. Science.2004,305:1587-1594.
[12] Zheng L, Kostrewa D, Bernèche S, Winkler FK, Li X-D.The crystal structure of AmtB of E. coli suggests a mechanism for ammonia transport. Proc Natl Acad Sci USA.2004, 101:17090-17095.
[13] Javelle A, Severi E, Thornton J, Merrick M. Ammonium sensing in Escherichia coli: role of the ammonium transporter AmtB and AmtB-GlnK complex formation. J. Biol. Chem. 2004, 279:8530-38.
[14] Zheng L, Kostrewa D, Bemeche S, Winkler FK, Li XD.The mechanism of ammonia transport based on the crystal structure of AmtB of Escherichia coli. Proc. Natl. Acad. Sci.USA.2004,101:17090-95.
[15] Nagami GT. Luminal secretion of ammonia in the mouse proximal tubule perfused in vitro. J. Clin. Invest. 1988,81:159-64.
[16] Nagami GT, Sonu CM, Kurokawa K. Ammonia production by isolated mouse proximal tubules perfused in vitro: effect of metabolic acidosis. J. Clin. Invest. 1986,78:124-29.
[17] Nagami GT.Effect of bath and luminal potassium concentration on ammonia production and secretion by mouse proximal tubules perfused in vitro. J. Clin. Invest. 1990, 86:32—39.
[18] Ambuhl PM, Amemiya M, Danczkay M, Lotscher M, Kaissling B, et al. Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney. Am.J.Physiol. Renal Physiol.1996,271:F917-25.
[19] Elkjar ML, Kwon TH, Wang W, Nielsen J, Knepper MA, et al. Altered expression of renal NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats. Am.J.Physiol.Renal Physiol.2002, 283:F1376-88.
[20] Nagami GT.Ammonia production and secretion by S3 proximal tubule segments from acidotic mice: role of ANG Ⅱ. Am.J.Physiol.Renal Physiol.2004, 287:F707-12.
[21] Choe H, Sackin H, Palmer LG.. Permeation properties of inward-rectifier potassium channels and their molecular determinants. J. Gen. Physiol.2000, 115:391-404.
[22] Volkl H, Lang F.Electrophysiology of ammonia transport in renal straight proximal tubules. Kidney Int. 1991, 40:1082-89.
[23] Haas M, Forbush B. The Na-K-Cl cotransporters. J.Bioenerg. Biomembr.1998, 30:161—72.
[24] Wall SM, Knepper MA, Hassell KA, Fischer MP, Shodeinde A, et al. Hypotension in NKCC1 null mice: role of the kidneys. Am. J. Physiol. Renal Physiol.2006, 290:F409-16.
[25] Meyer JW, Flagella M, Sutliff RL, Lorenz JN, Nieman ML, et al. Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na+-K+-2Cl-cotransporter. Am. J. Physiol.2002. Heart Circ. Physiol. 283:H1846-55.
[26] Ginns SM, Knepper MA, Ecelbarger CA, Terris J,He X, et al. Immunolocalization of the secretory isoform of Na-K-Cl cotransporter in rat renal intercalated cells. J. Am. Soc.Nephrol. 1996,7:2533-42.
[27] Wall SM, Fischer MP. Contribution of the Na+-K+-2C1- cotransporter (NKCC1) to transepithelial transport of H+, NH4+, K+, and Na+ in rat outer medullary collecting duct. J.Am. Soc. Nephrol.2002, 13:827-35.
[28]Wall SM,Trinh HN,Woodward KE.Heterogeneity of NH4~+ transport in mouse inner medullary collecting duct cells.Am.J.Physiol.Renal Physiol.1995,269:F536-44.
[29]Glanville M,Kingscote S,Thwaites DT,Simmons NL.Expression and role of sodium,potassium,chloride cotransport(NKCC1) in mouse inner medullary collecting duct(mIMCD-K2)epithelial cells.Pflugers Arch.2001,443:123-31.
[30]Wall SM.Ouabain reduces net acid secretion and increases pH_i by inhibiting NH_4~+uptake on rat tlMCD Na~+-K~+-ATPase.Am.J.Physiol.Renal Physiol.1997,273:F857-68.
[31]Ecelbarger CA,Terris J,Hoyer JR,Nielsen S,Wade JB,Knepper MA.Localization and regulation of the rat renal Na~+-K~+-2Cl~— cotransporter,BSC-1.Am.J.Physiol.Renal Physiol.1996,271:F619-28.
[32]Plotkin MD,Kaplan MR,Verlander JW,Lee WS,Brown D,et al.Localization of the thiazide sensitive Na-Cl cotransporter,rTSC1 in the rat kidney.Kidney Int 1996,50:174-83
[33]Kinne R,Kinne-Saffran E,Schutz H,Scholermann B.Ammonium transport in medullary thick ascending limb of rabbit kidney:involvement of the Na~+,K~+,Cl~—-cotransporter.J.Membr.Biol.1986,94:279-84.
[34]Attmane-Elakeb A,Mount DB,Sibella V,Vernimmen C,Hebert SC,Bichara M.by in vivo and in vitro metabolic acidosis of expression of rBSC-1,the Na~+-Stimulation K~+(NH_4~+)-2Cl~— cotranSporter of the rat medullary thick ascending limb.J.Biol.Chem.1998,273:33681-91.
[35]Attmane-Elakeb A,Sibella V,Vemimmen C,Belenfant X,Hebert SC,Bichara M.Regulation by glucocorticoids of expression and activity of rBSC1,the Na~+-K~+(NH_4~+)-2Cl~—cotransporter of medullary thick ascending limb.J.Biol.Chem.2000,275:33548-53.
[36]Ortiz PA.cAMP increases surface expression of NKCC2 in rat thick ascending limbs:role of VAMP.Am.J.Physiol.Renal Physiol.2006,290:F608-16.
[37]Martin DW.Structure-function relationships in the Na~+,K~+-pump.Semin.Nephrol.2005,25:282-91.
[38]Jorgensen PL.Sodium and potassium ion pump in kidney tubules.Physiol.Rev.1980,60:864-917.
[39]Kurtz I,Balaban RS.Ammonium as a substrate for Na~+-K~+-ATPase in rabbit proximal tubules.Am.J.Physiol.Renal Physiol.1986,250:F497-502.
[40]Wall SM,Koger LM.NH_4~+ transport mediated by Na~+-K~+-ATPase in rat inner medullary collecting duct.Am.J.Physiol.Renal Physiol.1994,267:F660-70.
[41]Knepper MA,Good DW,Burg MB.Mechanism of ammonia secretion by cortical collecting ducts of rabbits.Am.J.Physiol.Renal Physiol.1984,247:F729-38.
[42]Wall SM,Koge,r LM.NH4+ transport mediated by Na+-K+-ATPase in rat inner medullary collecting duct.Am.J.Physiol.Renal Physiol.1994,267:F660-70.
[43]Wall SM.NH_4~+ augments net acid-secretion by a ouabain-sensitive mechanism in isolated-perfused inner medullary collecting ducts.Am.J.Physiol.Renal Physiol.1996,270:F432-39.
[44]Wall SM.Mechanisms of NH_4~+ and NH_3 transport during hypokalemia.Acta Physiol.Stand.2003,179:325-30.
[45]Wall SM,Fischer MP,Kim GH,Nguyen BM,Hassell KA.In rat inner medullary collecting duct,NH_4~+ uptake by the Na,K-ATPase is increased during hypokalemia.Am.J.Physiol.Renal Physiol.2002,282:F91-102.
[46]Karim Z,Attmane-Elakeb A,Bichara M.Renal handling of NH_4~+ in relation to the contrc of acid-base balance by the kidney.J.Nephrol.2002,15(Suppl 5):S128-34.
[47]Attmane-Elakeb A,Boulanger H,Vernimmen C,Bichara M.Apical location and inhibition by arginine vasopressin of K~+/H~+ antiport of the medullary thick ascending limb of rat kidney.J.Biol.Chem..1997,272:25668-77.
[48]Cougnon M,Bouyer P,Jaisser F,Edelman A,Planelles G.1999.Ammonium transport b the colonic H~+-K~+-ATPase expressed in Xenopus oocytes.Am.J.Physiol.Cell Physiol.1999,277:C280-87.
[49]Codina J,Pressley TA,DuBose TD Jr.The colonic H~+,K~+-ATPase functions as a Na~+dependent K~+(NH_4~+)-ATPase in apical membranes from rat distal colon.J.Biol.Chem.1999,274:19693-98.
[50]Nakamura S,Amlal H,Galla JH,Soleimani M.NH_4~+ secretion in inner medullary collecting duct in potassium deprivation:role of colonic H~+-K~+-ATPase.Kidney Int.1999,56:2160-67.
[51]Swarts HGP,Koenderink JB,Willems PHGM,De Pont JJ.The non-gastric H,K-ATPase is oligomycin-sensitive and can function as an H~+,NH_4~+-ATPase.J.Biol.Chem.2005,280:33115-22.
[52]King LS,Kozono D,Agre P.From structure to disease:the evolving tale of aquaporin biology.Nat.Rev.Mol.Cell Biol.2004,5:687-98.
[53]Knepper MA.The aquaporin family of molecular water channels.Proc.Natl.Acad.Sci.USA,1994,91:6255-58.
[54]Nakhoul NL,Hering-Smith KS,Abdulnour-Nakhoul SM,Hamm LL.Transport of NH_3/NH in oocytes expressing aquaporin-1.Am.J.Physiol.Renal Physiol.2001,281:F255-63.
[55] Holm LM, Jahn TP, Moller AL, Schjoerring JK, Ferri D, et al.NH_3 and NH_4~+ permeability in aquaporin-expressing Xenopus oocytes. Pflügers Arch.2005,450:415-28.
[56] Beitz E, Wu B, Holm LM, Schultz JE, Zeuthen T. Point mutations in the aromatic/arginine region in aquaporin 1 allow passage of urea, glycerol, ammonia, and protons.Proc. Natl. Acad. Sci. USA.2006,103:269-74.
[57] Ma T, Song Y, Yang B, Gillespie A, Carlson EJ, et al. Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels. Proc. Natl. Acad. Sci. USA.2000,97:4386-91.
[58] Yang B, Song Y, Zhao D, Verkman AS. Phenotype analysis of aquaporin-8 null mice.Am. J. Physiol Cell Physiol.2005, 288:C1161-70.
[59] Yang B, Zhao D, Solenov E, Verkman AS. Evidence from knockout mice against physiologically significant aquaporin 8-facilitated ammonia transport. Am. J. Physiol. Cell Physiol.2006, 291:C417-23.
[60] Marini AM, Vissers S, Urrestarazu A, Andre B. Cloning and expression of the MEP1 gene encoding an ammonium transporter in Saccharomyces cerevisiae. EMBO J.1994,13:3456-3463.
[61] Ninnemann O, Jauniaux JC, Frommer WB.Identification of a high affinity NH4+ transporter from plants. EMBO J.1994 ,13:3464-3471.
[62] von Wiren N, Gazzarrini S, Gojon A, Frommer WB. The molecular physiology of ammonium uptake and retrieval. Curr Opin Plant Biol. 2000; 3:254-261.
[63] Gazzarrini S, Lejay L, Gojon A, Ninnemann O, Frommer WB, von Wiren N. Three functional transporters for constitutive, diurnally regulated, and starvation-induced uptake of ammonium into Arabidopsis roots. Plant Cell.1999,11:937-48.
[64] Marini AM, Soussi-Boudekou S, Vissers S, Andre B .A family of ammonium transporters in Saccharomyces cerevisiae. Mol Cell Biol.1997,17:4282—4293.
[65] Marini AM, Matassi G, Raynal V, Andre B, Cartron JP, Cherif-Zahar B. The human Rhesus-associated RhAG protein and a kidney homologue promote ammonium transport in yeast. Nat Genet.2000,26:341-344.
[66] Lorenz MC, Heitman J.The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO J .1998, 17:1236-1247.
[67] Marini AM, Urrestarazu A, Beauwens R, Andre B. The Rh (rhesus) blood group polypeptides are related to NH4+ transporters. Trends Biochem Sci. 1997,22:460-461.
[68] Liu Z, Chen Y, Mo R, et al. Characterization of human RhCG and mouse Rhcg as novel nonerythroid Rh glycoprotein homologues predominantly expressed in kidney and testis. J Biol Chem.2000,275:25641-25651.
[69] Liu Z, Peng J, Mo R, et al. Rh type B glycoprotein is a new member of the Rh superfamily and a putative ammonia transporter in mammals. J Biol Chem.2001,276:1424-1433.
[70] von Wiren N, Gazzarrini S, Gojon A, Frommer WB.The molecular physiology of ammonium uptake and retrieval. Curr. Opin. Plant Biol.2000, 3:254-61. [71] Westhoff CM, Ferreri-Jacobia M, Mak DD, Foskett JK.Identification of the erythrocyte Rh-blood group glycoprotein as a mammalian ammonium transporter. J. Biol. Chem.2002,277:12499-502.
[72] Ripoche P, Bertrand O, Gane P, Birkenmeier C, Colin Y, Cartron JP. Human Rhesus-associated glycoprotein mediates facilitated transport of NH_3 into red blood cells. Proc. Natl. Acad. Sci. USA.2004, 101:17222-27.
[73] Cartron JP.RH blood group system and molecular basis of Rh-deficiency. Baillieres Best Pract. Res. Clin. Haematol.1999, 12:655-89.
[74]Handlogten ME, Hong SP, Zhang L, Vander AW, Steinbaum ML, et al. Expression of the ammonia transporter proteins, Rh B Glycoprotein and Rh C Glycoprotein, in the intestinal tract. Am. J. Physiol. Gastrointest. Liver Physiol.2005, 288:G1036-47. [75] Quentin F, Eladari D, Cheval L, Lopez C, Goossens D, et al. RhBG and RhCG, the putative ammonia transporters, are expressed in the same cells in the distal nephron. J. Am. Soc. Nephrol.2003,14:545-54.
[76] Verlander JW, Miller RT, Frank AE, Royaux IE, Kim YH, Weiner ID. Localization of the ammonium transporter proteins, Rh B Glycoprotein and Rh C glycoprotein, in the mouse kidney. Am. J. Physiol. Renal Physiol.2003, 284:F323-37.
[77] Weiner ID, Miller RT, Verlander JW.Localization of the ammonium transporters, Rh B Glycoprotein and Rh C Glycoprotein in the mouse liver. Gastroenterology.2003,124:1432—40. [78] Seshadri RM, Klein JD, Kozlowski S, Sands JM, Kim YH, et al. Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis. Am. J. Physiol. Renal Physiol.2006, 290:F397-408.
[79] Kim YH, Verlander JW, Matthews SW, Kurtz I, Shin WK, et al. Intercalated cell H~+/OH~-transporter expression is reduced in Slc26a4 null mice. Am. J. Physiol. Renal Physiol.2005, 289:F1262-72.
[80] Chambrey R, Goossens D, Bourgeois S, Picard N, Bloch-Faure M, et al. Genetic ablation of Rhbg in mouse does not impair renal ammonium excretion. Am. J. Physiol. Renal Physiol.2005, 289:F1281-90.
[81]Eladari D,Cheval L,Quentin F,Bertrand O,Mouro I,et al.Expression of RhCG,a new putative NH_3/NH_4~+ transporter,along the rat nephron.J.Am.Soc.Nephrol.2002,13:1999-2008.
[82]Han KH,Croker BP,Clapp WL,Wemer D,Sahni M,Kim J,Kim HY,Handlogten ME,Weiner ID.Expression of the ammonia transporter,Rh C glycoprotein,in normal and neoplastic human kidney.J.Am.Soc.Nephrol.2006,17(10):2670-2679.
[83]Seshadri RM,Klein JD,Smith T,Sands JM,Handlogten ME,et al.Changes in the subcellular distribution of the ammonia transporter Rhcg,in response to chronic metabolic acidosis.Am.J.Physiol.Renal Physiol.2006,290:F1443-52.
[84]Ludewig U.Electroneutral ammonium transport by basolateral Rhesus B glycoprotein.J.Physiol.2004,559:751-59.
[2] Weiner, I David. The Rh gene family and renal ammonium transport. Curr Opin Nephrol Hypertens. 2004,13(5), 533-540.
[3] I. David Weiner, L. Lee Hamm. Molecular Mechanisms of Renal Ammonia Transport. Annual Review of Physiology.2007, 69: 317-340.
[4] Hamm LL, Simon EE. Roles and mechanisms of urinary buffer excretion. Am. J. Physiol.Renal Physiol. 1987, 253:F595-605.
[5] Sajo IM, Goldstein MB, Sonnenberg H, et al. Sites of ammonia addition to tubular fluid in rats with chronic metabolic acidosis. Kidney Int. 1982, 20:353-58.
[6] Knepper MA. NH_4~+ transport in the kidney. Kidney Int.1991,40: S95-S102.
[7] Tannen RL, Sahai A. Biochemical pathways and modulators of renal ammoniagenesis.Miner Electrolyte Metab, 1990,16:249-258.
[8] Nagami GT. Ammonia production and secretion by the proximal tubule. Am J Kidney Dis.1989,14:258-261.
[9] Simon EE, Merli C, Herndon J, et al. Effects of barium and 5-(N-ethyl-N-isopropyl)-amiloride on proximal tubule ammonia transport. Am J Physiol. 1992,262:F36-F39.
[10] Hamm LL, Simon EE. Ammonia transport in the proximal tubule. Min Electrolyte Metab.1990,16:283-290.
[11] Kikeri D, Sun A, Zeidel ML, et al. Cell membranes impermeable to NH3.Nature. 1989,339:478-480.
[12] Amlal H, Paillard M, Bichara M. NH4+ transport pathways in cells of medullary thick ascending limb of rat kidney. NH4+ conductance and K+/NH4+(H+) antiport. J Biol Chemistry. 1994,269:21962-21971.
[13] Attmane-Elakeb A, Amlal H, Bichara M. Ammonium carriers in medullary thick ascending limb. Am J Physiol Renal Physiol. 2001, 280:F1-F9.
[14] Bettinelli A, Ciarmatori S, Cesareo L, et al. Phenotypic variability in Bartter syndrome type I. Pediatric Nephrol, 2000,14:940-945.
[15] Rodriguez-Soriano J. Bartter and related syndromes: the puzzle is almost solved.Pediatric Nephrol .1998,12:315-327.
[16] Melton LB, Vanatta JC. Ammonia transport by the urinary bladder of Bufo marinus.Comp Biochem Physiol A Physiol. 1996,115:153-158.
[17] Wall SM. NH4+ augments net acid-secretion by a ouabain-sensitive mechanism in isolated-perfused inner medullary collecting ducts. Am J Physiol. 1996, 270:F432-F439.
[18] Dubois E, Grenson M. Methylamine/ammonia uptake systems in Saccharomyces cerevisiae: multiplicity and regulation. Mol Gen Genet. 1979,175:67-76.
[19] Marini AM, Vissers S, Urrestarazu A, et al. Cloning and expression of the MEP1 gene encoding an ammonium transporter in Saccharomyces cerevisiae. EMBO J.1994, 13:3456-3463.
[20] Ninnemann O, Jauniaux JC, Frommer WB. Identification of a high affinity NH4+ transporter from plants. EMBO J.1994, 13:3464-3471.
[21] Marini AM, Soussi-Boudekou S, Vissers S, et al. A family of ammonium transporters in Saccharomyces cerevisiae. Mol Cell Biol.1997; 17:4282-4293.
[22] von Wiren N, Gazzarrini S, Gojon A, et al. The molecular physiology of ammonium uptake and retrieval. Curr Opin Plant Biol. 2000; 3:254-261.
[23] Marini AM, Urrestarazu A, Beauwens R, et al. The Rh (rhesus) blood group polypeptides are related to NH4+ transporters. Trends Biochem Sci.1997, 22:460-461.
[24] Liu Z, Peng J, Mo R, Hui CC, et al. Rh type B glycoprotein is a new member of the Rh superfamily and a putative ammonia transporter in mammals. J Biol Chem.2001, 276: 1424-1433.
[25] Liu Z, Chen Y, Mo R, et al. Characterization of human RhCG and mouse Rhcg as novel nonerythroid Rh glycoprotein homologues predominantly expressed in kidney and testis. J Biol Chem. 2000, 275: 25641-25651.
[26] Ludewig U. Electroneutral ammonium transport by basolateral Rhesus B glycoprotein. J Physiol. 2004, 559: 751-759.
[27] Mak DD, Dang B, Weiner ID, et al. Characterization of transport by the kidney Rh glycoproteins, RhBG and RhCG. Am J Physiol Renal Physiol .2006, 290(2):F297-305.
[28] Nakhoul NL, DeJong H, Abdulnour-Nakhoul SM, et al. Characteristics of renal Rhbg as an NH_4~+ transporter. Am J Physiol Renal Physiol .2005, 288: F170-F181.
[29] Planelles G. Ammonium homeostasis and human Rhesus glycoproteins. Nephron Physio.2007, 105:11-7,2007
[30] Handlogten ME, Hong SP, Zhang L, et al. Expression of the ammonia transporter proteins, Rh B glycoprotein and Rh C glycoprotein, in the intestinal tract. Am J Physiol Gastrointest Liver Physiol.2005, 288 : G1036 -G1047.
[31] Verlander JW, Miller RT, Frank AE, et al. Localization of the ammonium transporter proteins, RhBG and RhCG, in mouse kidney. Am J Physiol Renal Physiol.2003, 284: F323-F337.
[32] Eladari D, Cheval L, Quentin F, et al. Expression of RhCG, a new putative NH(3)/NH(4)(+) transporter, along the rat nephron. J Am Soc Nephrol. 2002,13:1999-2008
[33] Nielsen S, Fr(?)ki?r J, Marples D, et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev.2002, 82(1):205-44.
[34] Handlogten ME, Hong SP, Zhang L, et al. Expression of the ammonia transporter proteins, Rh B glycoprotein and Rh C glycoprotein, in the intestinal tract. Am J Physiol Gastrointest Liver Physiol. 2005, 288 : G1036 -G1047.
[35] Weiner ID, Miller RT, and Verlander JW. Localization of the ammonium transporters,Rh B glycoprotein and Rh C glycoprotein in the mouse liver. Gastroenterology. 2003, 124:1432-1440.
[36] Weiner ID.Expression of the non-erythroid Rh glycoproteins in mammalian tissues. Transfus Clin Biol. 2006,13:159-63.
[37] Han KH, Croker BP, Clapp WL, et al. Expression of the ammonia transporter, Rh C glycoprotein, in normal and neoplastic human kidney. J. Am. Soc. Nephrol. 2006,17(10):2670-2679.
[38] Seshadri RM, Klein JD, Kozlowski S, et al. Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis. Am J Physiol Renal Physiol. 2006, 290 : F397 -F408.
[39] Gazzarrini S, Lejay L, Gojon A, et al. Three functional transporters for constitutive,diumally regulated, and starvation-induced uptake of ammonium into Arabidopsis roots. Plant Cell. 1999, 11:937-48.
[40] Lorenz MC, Heitman J. The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO J.1998,17:1236-1247.
[1] Isozaki T, Verlander JW, and Sands JM. Low protein diet alters urea transport and cell structure in rat initial inner medullary collecting duct. J. Clin. Invest 1993, 92: 2448-2457.
[2] Isozaki T, Gillin AG, Swanson CE, et al. Protein restriction sequentially induces new urea transport processes in rat initial IMCDs. Am.J. Physiol.1994,266:F756-F761.
[3] Peil AE, Stolte H, and Schmidt-Nielsen B. Uncoupling of glomerular and tubular regulations of urea excretion in rat. Am. J. Physiol. 1990, 258: F1666-F1674.
[4] Klein JD, Sands JM, Qian L, et al. Upregulation of urea transporter UT-A2 and water channels AQP2 and AQP3 in mice lacking urea transporter UT-B. J Am Soc Nephrol.2004,15:1161-1167.
[5] Handlogten ME, Hong SP, Westhoff CM, et al. Basolateral ammonium transport by the mouse inner medullary collecting duct cell (mIMCD-3). Am J Physiol Renal Physiol.2004,287:F628-F638.
[6] Verlander JW, Miller RT, Frank AE, et al. Localization of the ammonium transporter proteins, RhBG and RhCG, in mouse kidney. Am J Physiol Renal Physiol. 2003, 284: F323-F337.
[7] Weiner ID, Miller RT, and Verlander JW. Localization of the ammonium transporters, Rh B glycoprotein and Rh C glycoprotein in the mouse liver. Gastroenterology. 2003,124: 1432-1440.
[8] Handlogten ME, Hong SP, Westhoff CM, et al. Apical ammonia transport by the mouse inner medullary collecting duct, mIMCD-3, cell. Am J Physiol Renal Physiol.2005, 289:F347-F358.
[9] Handlogten ME, Hong SP, Zhang L, et al. Expression of the ammonia transporter proteins,Rh B glycoprotein and Rh C glycoprotein, in the intestinal tract. Am J Physiol Gastrointest Liver Physiol. 2005,288 : G1036 -G1047.
[10] Seshadri RM, Klein JD, Kozlowski S, et al. Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis. Am J Physiol Renal Physiol.2006, 290 : F397 -F408.
[11] Quentin F, Eladari D, Cheval L, et al. RhBG and RhCG, the putative ammonia transporters, are expressed in the same cells in the distal nephron. J Am Soc Nephrol.2003, 14:545-554.
[12] Eladari D, Cheval L, Quentin F, et al. Expression of RhCG, a new putative NH(3)/NH(4)(+) transporter, along the rat nephron. J Am Soc Nephrol.2002,13:1999-2008.
[13] Marini AM, Urrestarazu A, Beauwens R, et al. The Rh (rhesus) blood group polypeptides are related to NH4+ transporters. Trends Biochem Sci. 1997, 22:460-461.
[14] Marini AM, Matassi G, Raynal V, et al. The human rhesus-associated RhAG protein and a kidney homologue promote ammonium transport in yeast. Nat Genet 2000,26:341-344.
[15] Liu Z, Chen Y, Mo R, et al. Characterization of human RhCG and mouse Rhcg as novel nonerythroid Rh glycoprotein homologues predominantly expressed in kidney and testis. J Biol Chem.2000, 27-5:25641-25651.
[16] Liu Z, Peng J, Mo R, et al. Rh type B glycoprotein is a new member of the Rh superfamily and a putative ammonia transporter in mammals. J Biol Chem.2001, 276:1424-1433.
[17] I. David Weiner, L. Lee Hamm. Molecular Mechanisms of Renal. Ammonia Transport.Annual Review of Physiology.2007, 69: 317-340.
[18] Lopez C, Metral S, Eladari D, Drevensek S, Gane P, et al. The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells. J. Biol. Chem. 2004, 280:8221-28
[19] Chambrey R, Goossens D, Bourgeois S, et al . Genetic ablation of Rhbg in mouse does not impair renal ammonium excretion. Am. J. Physiol Renal Physiol. 2005, 289:F1281-F1290.
[20] Kim YH, Verlander JW, Matthews SW, et al, Everett LA, Green ED, Nielsen S, Wall SM. Intercalated cell H~+/OH~- transporter expression is reduced in Slc26a4 null mice. Am. J.Physiol. Renal Physiol .2005, 289:F1262-72.
[21] Gazzarrini S, Lejay L, Gojon A, et al. Three functional transporters for constitutive, diurnally regulated, and starvation-induced uptake of ammonium into Arabidopsis roots. Plant Cell. 1999, 11:937-48.
[22] von Wiren N, Gazzarrini S, Gojon A, et al et al. The molecular physiology of ammonium uptake and retrieval. Curr Opin Plant Biol. 2000, 3:254-61.
[23] Marini AM, Soussi-Boudekou S, Vissers S, et al. A family of ammonium transporters in Saccharomyces cerevisiae. Mol Cell Biol. 1997,17:4282-4293.
[24] Peng J and Huang CH. Rh proteins vs Amt proteins: an organismal and phylogenetic perspective on CO_2 and NH_3 gas channels. Transfus Clin Biol.2006,13:85-94.
[25] Mak DD, Dang B, Weiner ID, et al. 2006. Characterization of transport by the kidney Rh glycoproteins, RhBG and RhCG. Am. J. Physiol. Renal Physiol. 290:F297-305.
[26] Ludewig U. 2004. Electroneutral ammonium transport by basolateral Rhesus B glycoprotein. J. Physiol. 559:751-59.
[27] Zidi-Yahiaoui N, Mouro-Chanteloup I, D'Ambrosio AM, et al. Human Rhesus B and Rhesus C glycoproteins: properties of facilitated ammonium transport in recombinant kidney cells. Biochem. J.2005, 391:33-40.
[28] Palkova Z, Janderova B., Gabriel J, et al. Ammonia mediates communication between yeast colonies. Nature. 1997, 390:532-536.
[29] Lorenz MC, and Heitman J. The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO J. 1998, 17,1236-1247.
[30] Johansson FK, Brodd J, Eklof C, et al. Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging. Proc Natl Acad Sci USA.2004,101: 11334-11337.
[31] Conroy MJ, Jamieson SJ, Blakey D, et al. Electron and atomic force microscopy of the trimeric ammonium transporter AmtB. EMBO Rep. 2004, 5:1153-1158.
[32] Khademi S, O'Connell J Ⅲ, Remis J, et al. Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 (?). Science.2004, 305:1587-1594.
[33] Zheng L, Kostrewa D, Berneche S, et al. The mechanism of ammonia transport based on the crystal structure of AmtB of Escherichia coli. Proc Natl. Acad Sci .2004,101:17090-95.
[34] Marini AM, Boeckstaens M, Benjelloun F. et al. Structural involvement in substrate recognition of an essential aspartate residue conserved in Mep/Amt and Rh-type ammonium transporters. Curr Genet.2006, 49(6):364-74.
[35] Conroy MJ, Jamieson SJ, Blakey D, et al, Merrick M, Bullough PA. Electron and atomic force microscopy of the trimeric ammonium transporter AmtB. EMBO Rep. 5:1153-1158,2004.
[36] Bastani B, Haragsim L. Immunocytochemistry of renal H-ATPase. Miner Electrolyte Metab.1996, 22(5-6):382-95.
[37] Nielsen S, DiGiovanni SR, Christensen EI, et al. Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci USA. 1993, 90: 11663-11667.
[38] Nielsen S, Fr(?)ki?r J, Marples D, et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002, 82(1):205-44.
[39] Han KH, Croker BP, Clapp WL, et al. Expression of the ammonia transporter, Rh C glycoprotein, in normal and neoplastic human kidney. J. Am. Soc. Nephrol.2006,17(10):2670-2679.
[40] Marples D, Knepper MA, Christensen EI, et al. Redistribution of aquaporin-2 water channels induced by vasopressin in rat kidney inner medullary collecting duct. Am J Physiol Cell Physiol. 269: C655-C664,1995.
[41] Lopez C, Métral S, Eladari, et al. The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells. J Biol Chem.2005, 280:8221-8228.
[42] Star RA, Kurtz I, Mejia R, et al. Disequilibrium pH and ammonia transport in isolated perfused cortical collecting ducts. Am. J. Physiol(Renal Fluid Electrolyte Physiol ).1987,253:F1232-F1242.
[42] Yip KP and Kurtz I. NH_3 permeability of principal cells and intercalated cells measured by confocal fluorescence imaging. Am J Physiol Renal Fluid Electrolyte Physiol. 1995, 269:F545-F550.
[43] Planelles G. Ammonium homeostasis and human Rhesus glycoproteins. Nephron Physiol.2007, 105:11-7.
[44] Weiner ID.Expression of the non-erythroid Rh glycoproteins in mammalian tissues.Transfus. Clin. Biol. 2006,13:159-63.
[45] Seshadri RM, Klein JD, Smith T, et al. Changes in the subcellular distribution of the ammonia transporter Rhcg, in response to chronic metabolic acidosis. Am. J. Physiol. Renal Physiol. 2006, 290:F1443-52.
[46] Bakouh N, Benjelloun F, Hulin P, et al. NH_3 is involved in the NH_4~+ transport induced by the functional expression of the human Rh C glycoprotein. J. Biol. Chem. 2004,279:15975-83.
[47] Nakhoul NL, Palmer SA, Abdulnour-Nakhoul S, et al. Ammonium transport in oocytes expressing Rheg. FASEB J.2002, 16(4):A53 (Abstr.)
[48] Weiner ID.The Rh gene family and renal ammonium transport. Curr. Opin. Nephrol.Hypertens. 2004,13:533-40.
[49] Bakouh N, Benjelloun F, Hulin P, et al et al. NH_3 is involved in the NH_4~+ transport induced by the functional expression of the human Rh C glycoprotein. J Biol Chem.2004, 279:15975-15983.
[1] Haussinger D, Lamers WH, Moorman AF. Hepatocyte heterogeneity in the metabolism of amino acids and ammonia. Enzyme. 1992, 46:72-93.
[2] Kikeri D, Sun A, Zeidel ML, Hebert SC. Cell membranes impermeable to NH_3. Nature. 1989,339:478-80.
[3] Amlal H, Paillard M, Bichara M.NH_4~+ transport pathways in cells of medullary thick ascending limb of rat kidney. NH_4~+ conductance and K~+/NH_4~+ (H~+) antiport. J. Biol. Chem. 1994, 269:21962-71.
[4] Attmane-Elakeb A, Amlal H, Bichara M. Ammonium carriers in medullary thick ascending limb. Am. J. Physiol. Renal Physiol.2001, 280:F1-9.
[5] Flessner MF, Mejia R, Knepper MA. Ammonium and bicarbonate transport in isolated perfused rodent long-loop thin descending limbs. Am. J. Physiol. 1993, 264:F388-96. [6] Mejia R, Flessner MF, Knepper MA. Model of ammonium and bicarbonate transport along LDL: implications for alkalinization of luminal fluid. Am. J. Physiol. Renal Physiol. 1993, 264:F397-403.
[7] DuBose TD Jr, Good DW, Hamm LL, Wall SM. Ammonium transport in the kidney: new physiological concepts and their clinical implications. J. Am. Soc. Nephrol. 1991,1:1193-203 [8] Hamm LL, Simon EE. Roles and mechanisms of urinary buffer excretion. Am. J. Physiol. Renal Physiol. 1987, 253:F595-605.
[9] Handlogten ME, Hong SP, Westhoff CM, Weiner ID.Basolateral ammonium transport by the mouse inner medullary collecting duct cell (mIMCD-3). Am. J. Physiol. Renal Physiol.2004, 287:F628-38.
[10] Handlogten ME, Hong SP, Westhoff CM, Weiner ID. Apical ammonia transport by the mouse inner medullary collecting duct cell (mIMCD-3).Am J Physiol Renal Physiol.2005,289(2):F347-58.
[11] Khademi S, O'Connell J Ⅲ, Remis J, Robles-Colmenares Y, Miercke LJ, Stroud RM. Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 A. Science.2004,305:1587-1594.
[12] Zheng L, Kostrewa D, Bernèche S, Winkler FK, Li X-D.The crystal structure of AmtB of E. coli suggests a mechanism for ammonia transport. Proc Natl Acad Sci USA.2004, 101:17090-17095.
[13] Javelle A, Severi E, Thornton J, Merrick M. Ammonium sensing in Escherichia coli: role of the ammonium transporter AmtB and AmtB-GlnK complex formation. J. Biol. Chem. 2004, 279:8530-38.
[14] Zheng L, Kostrewa D, Bemeche S, Winkler FK, Li XD.The mechanism of ammonia transport based on the crystal structure of AmtB of Escherichia coli. Proc. Natl. Acad. Sci.USA.2004,101:17090-95.
[15] Nagami GT. Luminal secretion of ammonia in the mouse proximal tubule perfused in vitro. J. Clin. Invest. 1988,81:159-64.
[16] Nagami GT, Sonu CM, Kurokawa K. Ammonia production by isolated mouse proximal tubules perfused in vitro: effect of metabolic acidosis. J. Clin. Invest. 1986,78:124-29.
[17] Nagami GT.Effect of bath and luminal potassium concentration on ammonia production and secretion by mouse proximal tubules perfused in vitro. J. Clin. Invest. 1990, 86:32—39.
[18] Ambuhl PM, Amemiya M, Danczkay M, Lotscher M, Kaissling B, et al. Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney. Am.J.Physiol. Renal Physiol.1996,271:F917-25.
[19] Elkjar ML, Kwon TH, Wang W, Nielsen J, Knepper MA, et al. Altered expression of renal NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats. Am.J.Physiol.Renal Physiol.2002, 283:F1376-88.
[20] Nagami GT.Ammonia production and secretion by S3 proximal tubule segments from acidotic mice: role of ANG Ⅱ. Am.J.Physiol.Renal Physiol.2004, 287:F707-12.
[21] Choe H, Sackin H, Palmer LG.. Permeation properties of inward-rectifier potassium channels and their molecular determinants. J. Gen. Physiol.2000, 115:391-404.
[22] Volkl H, Lang F.Electrophysiology of ammonia transport in renal straight proximal tubules. Kidney Int. 1991, 40:1082-89.
[23] Haas M, Forbush B. The Na-K-Cl cotransporters. J.Bioenerg. Biomembr.1998, 30:161—72.
[24] Wall SM, Knepper MA, Hassell KA, Fischer MP, Shodeinde A, et al. Hypotension in NKCC1 null mice: role of the kidneys. Am. J. Physiol. Renal Physiol.2006, 290:F409-16.
[25] Meyer JW, Flagella M, Sutliff RL, Lorenz JN, Nieman ML, et al. Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na+-K+-2Cl-cotransporter. Am. J. Physiol.2002. Heart Circ. Physiol. 283:H1846-55.
[26] Ginns SM, Knepper MA, Ecelbarger CA, Terris J,He X, et al. Immunolocalization of the secretory isoform of Na-K-Cl cotransporter in rat renal intercalated cells. J. Am. Soc.Nephrol. 1996,7:2533-42.
[27] Wall SM, Fischer MP. Contribution of the Na+-K+-2C1- cotransporter (NKCC1) to transepithelial transport of H+, NH4+, K+, and Na+ in rat outer medullary collecting duct. J.Am. Soc. Nephrol.2002, 13:827-35.
[28]Wall SM,Trinh HN,Woodward KE.Heterogeneity of NH4~+ transport in mouse inner medullary collecting duct cells.Am.J.Physiol.Renal Physiol.1995,269:F536-44.
[29]Glanville M,Kingscote S,Thwaites DT,Simmons NL.Expression and role of sodium,potassium,chloride cotransport(NKCC1) in mouse inner medullary collecting duct(mIMCD-K2)epithelial cells.Pflugers Arch.2001,443:123-31.
[30]Wall SM.Ouabain reduces net acid secretion and increases pH_i by inhibiting NH_4~+uptake on rat tlMCD Na~+-K~+-ATPase.Am.J.Physiol.Renal Physiol.1997,273:F857-68.
[31]Ecelbarger CA,Terris J,Hoyer JR,Nielsen S,Wade JB,Knepper MA.Localization and regulation of the rat renal Na~+-K~+-2Cl~— cotransporter,BSC-1.Am.J.Physiol.Renal Physiol.1996,271:F619-28.
[32]Plotkin MD,Kaplan MR,Verlander JW,Lee WS,Brown D,et al.Localization of the thiazide sensitive Na-Cl cotransporter,rTSC1 in the rat kidney.Kidney Int 1996,50:174-83
[33]Kinne R,Kinne-Saffran E,Schutz H,Scholermann B.Ammonium transport in medullary thick ascending limb of rabbit kidney:involvement of the Na~+,K~+,Cl~—-cotransporter.J.Membr.Biol.1986,94:279-84.
[34]Attmane-Elakeb A,Mount DB,Sibella V,Vernimmen C,Hebert SC,Bichara M.by in vivo and in vitro metabolic acidosis of expression of rBSC-1,the Na~+-Stimulation K~+(NH_4~+)-2Cl~— cotranSporter of the rat medullary thick ascending limb.J.Biol.Chem.1998,273:33681-91.
[35]Attmane-Elakeb A,Sibella V,Vemimmen C,Belenfant X,Hebert SC,Bichara M.Regulation by glucocorticoids of expression and activity of rBSC1,the Na~+-K~+(NH_4~+)-2Cl~—cotransporter of medullary thick ascending limb.J.Biol.Chem.2000,275:33548-53.
[36]Ortiz PA.cAMP increases surface expression of NKCC2 in rat thick ascending limbs:role of VAMP.Am.J.Physiol.Renal Physiol.2006,290:F608-16.
[37]Martin DW.Structure-function relationships in the Na~+,K~+-pump.Semin.Nephrol.2005,25:282-91.
[38]Jorgensen PL.Sodium and potassium ion pump in kidney tubules.Physiol.Rev.1980,60:864-917.
[39]Kurtz I,Balaban RS.Ammonium as a substrate for Na~+-K~+-ATPase in rabbit proximal tubules.Am.J.Physiol.Renal Physiol.1986,250:F497-502.
[40]Wall SM,Koger LM.NH_4~+ transport mediated by Na~+-K~+-ATPase in rat inner medullary collecting duct.Am.J.Physiol.Renal Physiol.1994,267:F660-70.
[41]Knepper MA,Good DW,Burg MB.Mechanism of ammonia secretion by cortical collecting ducts of rabbits.Am.J.Physiol.Renal Physiol.1984,247:F729-38.
[42]Wall SM,Koge,r LM.NH4+ transport mediated by Na+-K+-ATPase in rat inner medullary collecting duct.Am.J.Physiol.Renal Physiol.1994,267:F660-70.
[43]Wall SM.NH_4~+ augments net acid-secretion by a ouabain-sensitive mechanism in isolated-perfused inner medullary collecting ducts.Am.J.Physiol.Renal Physiol.1996,270:F432-39.
[44]Wall SM.Mechanisms of NH_4~+ and NH_3 transport during hypokalemia.Acta Physiol.Stand.2003,179:325-30.
[45]Wall SM,Fischer MP,Kim GH,Nguyen BM,Hassell KA.In rat inner medullary collecting duct,NH_4~+ uptake by the Na,K-ATPase is increased during hypokalemia.Am.J.Physiol.Renal Physiol.2002,282:F91-102.
[46]Karim Z,Attmane-Elakeb A,Bichara M.Renal handling of NH_4~+ in relation to the contrc of acid-base balance by the kidney.J.Nephrol.2002,15(Suppl 5):S128-34.
[47]Attmane-Elakeb A,Boulanger H,Vernimmen C,Bichara M.Apical location and inhibition by arginine vasopressin of K~+/H~+ antiport of the medullary thick ascending limb of rat kidney.J.Biol.Chem..1997,272:25668-77.
[48]Cougnon M,Bouyer P,Jaisser F,Edelman A,Planelles G.1999.Ammonium transport b the colonic H~+-K~+-ATPase expressed in Xenopus oocytes.Am.J.Physiol.Cell Physiol.1999,277:C280-87.
[49]Codina J,Pressley TA,DuBose TD Jr.The colonic H~+,K~+-ATPase functions as a Na~+dependent K~+(NH_4~+)-ATPase in apical membranes from rat distal colon.J.Biol.Chem.1999,274:19693-98.
[50]Nakamura S,Amlal H,Galla JH,Soleimani M.NH_4~+ secretion in inner medullary collecting duct in potassium deprivation:role of colonic H~+-K~+-ATPase.Kidney Int.1999,56:2160-67.
[51]Swarts HGP,Koenderink JB,Willems PHGM,De Pont JJ.The non-gastric H,K-ATPase is oligomycin-sensitive and can function as an H~+,NH_4~+-ATPase.J.Biol.Chem.2005,280:33115-22.
[52]King LS,Kozono D,Agre P.From structure to disease:the evolving tale of aquaporin biology.Nat.Rev.Mol.Cell Biol.2004,5:687-98.
[53]Knepper MA.The aquaporin family of molecular water channels.Proc.Natl.Acad.Sci.USA,1994,91:6255-58.
[54]Nakhoul NL,Hering-Smith KS,Abdulnour-Nakhoul SM,Hamm LL.Transport of NH_3/NH in oocytes expressing aquaporin-1.Am.J.Physiol.Renal Physiol.2001,281:F255-63.
[55] Holm LM, Jahn TP, Moller AL, Schjoerring JK, Ferri D, et al.NH_3 and NH_4~+ permeability in aquaporin-expressing Xenopus oocytes. Pflügers Arch.2005,450:415-28.
[56] Beitz E, Wu B, Holm LM, Schultz JE, Zeuthen T. Point mutations in the aromatic/arginine region in aquaporin 1 allow passage of urea, glycerol, ammonia, and protons.Proc. Natl. Acad. Sci. USA.2006,103:269-74.
[57] Ma T, Song Y, Yang B, Gillespie A, Carlson EJ, et al. Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels. Proc. Natl. Acad. Sci. USA.2000,97:4386-91.
[58] Yang B, Song Y, Zhao D, Verkman AS. Phenotype analysis of aquaporin-8 null mice.Am. J. Physiol Cell Physiol.2005, 288:C1161-70.
[59] Yang B, Zhao D, Solenov E, Verkman AS. Evidence from knockout mice against physiologically significant aquaporin 8-facilitated ammonia transport. Am. J. Physiol. Cell Physiol.2006, 291:C417-23.
[60] Marini AM, Vissers S, Urrestarazu A, Andre B. Cloning and expression of the MEP1 gene encoding an ammonium transporter in Saccharomyces cerevisiae. EMBO J.1994,13:3456-3463.
[61] Ninnemann O, Jauniaux JC, Frommer WB.Identification of a high affinity NH4+ transporter from plants. EMBO J.1994 ,13:3464-3471.
[62] von Wiren N, Gazzarrini S, Gojon A, Frommer WB. The molecular physiology of ammonium uptake and retrieval. Curr Opin Plant Biol. 2000; 3:254-261.
[63] Gazzarrini S, Lejay L, Gojon A, Ninnemann O, Frommer WB, von Wiren N. Three functional transporters for constitutive, diurnally regulated, and starvation-induced uptake of ammonium into Arabidopsis roots. Plant Cell.1999,11:937-48.
[64] Marini AM, Soussi-Boudekou S, Vissers S, Andre B .A family of ammonium transporters in Saccharomyces cerevisiae. Mol Cell Biol.1997,17:4282—4293.
[65] Marini AM, Matassi G, Raynal V, Andre B, Cartron JP, Cherif-Zahar B. The human Rhesus-associated RhAG protein and a kidney homologue promote ammonium transport in yeast. Nat Genet.2000,26:341-344.
[66] Lorenz MC, Heitman J.The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO J .1998, 17:1236-1247.
[67] Marini AM, Urrestarazu A, Beauwens R, Andre B. The Rh (rhesus) blood group polypeptides are related to NH4+ transporters. Trends Biochem Sci. 1997,22:460-461.
[68] Liu Z, Chen Y, Mo R, et al. Characterization of human RhCG and mouse Rhcg as novel nonerythroid Rh glycoprotein homologues predominantly expressed in kidney and testis. J Biol Chem.2000,275:25641-25651.
[69] Liu Z, Peng J, Mo R, et al. Rh type B glycoprotein is a new member of the Rh superfamily and a putative ammonia transporter in mammals. J Biol Chem.2001,276:1424-1433.
[70] von Wiren N, Gazzarrini S, Gojon A, Frommer WB.The molecular physiology of ammonium uptake and retrieval. Curr. Opin. Plant Biol.2000, 3:254-61. [71] Westhoff CM, Ferreri-Jacobia M, Mak DD, Foskett JK.Identification of the erythrocyte Rh-blood group glycoprotein as a mammalian ammonium transporter. J. Biol. Chem.2002,277:12499-502.
[72] Ripoche P, Bertrand O, Gane P, Birkenmeier C, Colin Y, Cartron JP. Human Rhesus-associated glycoprotein mediates facilitated transport of NH_3 into red blood cells. Proc. Natl. Acad. Sci. USA.2004, 101:17222-27.
[73] Cartron JP.RH blood group system and molecular basis of Rh-deficiency. Baillieres Best Pract. Res. Clin. Haematol.1999, 12:655-89.
[74]Handlogten ME, Hong SP, Zhang L, Vander AW, Steinbaum ML, et al. Expression of the ammonia transporter proteins, Rh B Glycoprotein and Rh C Glycoprotein, in the intestinal tract. Am. J. Physiol. Gastrointest. Liver Physiol.2005, 288:G1036-47. [75] Quentin F, Eladari D, Cheval L, Lopez C, Goossens D, et al. RhBG and RhCG, the putative ammonia transporters, are expressed in the same cells in the distal nephron. J. Am. Soc. Nephrol.2003,14:545-54.
[76] Verlander JW, Miller RT, Frank AE, Royaux IE, Kim YH, Weiner ID. Localization of the ammonium transporter proteins, Rh B Glycoprotein and Rh C glycoprotein, in the mouse kidney. Am. J. Physiol. Renal Physiol.2003, 284:F323-37.
[77] Weiner ID, Miller RT, Verlander JW.Localization of the ammonium transporters, Rh B Glycoprotein and Rh C Glycoprotein in the mouse liver. Gastroenterology.2003,124:1432—40. [78] Seshadri RM, Klein JD, Kozlowski S, Sands JM, Kim YH, et al. Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis. Am. J. Physiol. Renal Physiol.2006, 290:F397-408.
[79] Kim YH, Verlander JW, Matthews SW, Kurtz I, Shin WK, et al. Intercalated cell H~+/OH~-transporter expression is reduced in Slc26a4 null mice. Am. J. Physiol. Renal Physiol.2005, 289:F1262-72.
[80] Chambrey R, Goossens D, Bourgeois S, Picard N, Bloch-Faure M, et al. Genetic ablation of Rhbg in mouse does not impair renal ammonium excretion. Am. J. Physiol. Renal Physiol.2005, 289:F1281-90.
[81]Eladari D,Cheval L,Quentin F,Bertrand O,Mouro I,et al.Expression of RhCG,a new putative NH_3/NH_4~+ transporter,along the rat nephron.J.Am.Soc.Nephrol.2002,13:1999-2008.
[82]Han KH,Croker BP,Clapp WL,Wemer D,Sahni M,Kim J,Kim HY,Handlogten ME,Weiner ID.Expression of the ammonia transporter,Rh C glycoprotein,in normal and neoplastic human kidney.J.Am.Soc.Nephrol.2006,17(10):2670-2679.
[83]Seshadri RM,Klein JD,Smith T,Sands JM,Handlogten ME,et al.Changes in the subcellular distribution of the ammonia transporter Rhcg,in response to chronic metabolic acidosis.Am.J.Physiol.Renal Physiol.2006,290:F1443-52.
[84]Ludewig U.Electroneutral ammonium transport by basolateral Rhesus B glycoprotein.J.Physiol.2004,559:751-59.