肺微血管内皮细胞β-AR和GRK2与重症急性胰腺炎肺损伤关系的实验研究
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摘要
目的建立SD大鼠重症急性胰腺炎(SAP)动物模型,观察重症急性胰腺炎致急性肺损伤时肺组织的病理改变,观察肺微血管内皮细胞(PMVEC)β受体(β-AR)和肺组织G蛋白偶联受体激酶2(GRK2)与SAP肺损伤的关系以及甲基强的松龙的保护作用。
方法采用雄性SD大鼠,随机分设对照组、实验组和干预组。对照组剖腹后十二指肠翻动找到胰腺随即关腹;实验组予5%牛磺胆酸钠(1 ml/kg)逆行胰胆管注射,制备SAP模型;干预组在制模后30 min臀部肌肉注射甲强龙(30mg/kg)。观察制模后6h和12h的相关指标:胰腺和肺大体病理改变(肉眼观),胰腺和肺镜下病理改变(HE染色),肺组织含水量(干湿重法),肺微血管内皮细胞的β-AR的最大结合容量Bmax和平衡解离常数Kd(放射配基结合实验),肺组织GRK2表达(免疫荧光),血清IL-6水平变化(ELISA法)。
结果
1实验组肺组织含水量在制模后6h可见明显升高,12h更为明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
2.实验组β-AR最大结合容量Bmax在制模后6h可见明显降低,12h降低更为明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
3.实验组β-AR平衡解离常数Kd在制模后6h可见升高,12h更加明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
4.要验组肺组织GRK2表达在制模后6h即有升高,12h更加明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
5.实验组血清IL-6水平在制模后6h可见升高,12h更加明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
6.干预组与实验组比较:在6h,肺组织含水量减少,β-AR最大结合容量Bmax明显升高,β-AR平衡解离常数Kd可见降低,GRK2的表达显著降低,IL-6水平降低,有显著性差异(P＜0.05);在12h,各项指标变化更加明显,有显著性差异(P＜0.05)。
结论
1、SAP模型在制模后6h发现有肺损伤,12h更加严重。
2、SAP模型肺微血管内皮细胞的β-AR是下调的。
3、SAP模型肺组织GRK2表达显著增加,这可能是β-AR下调的重要机制,并与β-AR共同参与了SAP肺损伤的病理过程。
4、甲强龙可以上调β-AR,降低SAP模型肺组织GRK2表达,减轻肺水肿,改善肺内炎症反应,降低血清IL-6水平,减轻大鼠SAP肺损伤的严重程度,对SAP肺损伤具有保护作用。
Objective To investigate pathological changes,variation ofβ-AR in pulmonary microvascular endothelial cells and variation of GRK2 in lung and to explore the therapeutic effect of methyprednisolone in severe acute pancreatitis-associated lung injury model in rats.
Methods Male SD rats were divided into three groups randomly:the control group,the experimental group and the intervention group.In the control group, laparotomy were performed,duodenum and pancreas were flipped only.In the experimental group,acute necrotizing pancreatitis model was induced in rats by retrograde injection of 5%sodium taurocholate into biliopancreatic duct.In the intervention group,methylprednisolone(30mg/kg)was injected into rump musle of rats after models were developed.At 6 and 12 hours after model were developed, the maximum binding capacity(Bmax)and the Kd value of PMVECβ-AR was detected in lung by means of radioactive ligand binding assay.GRK2 expression was detected in lung by means of immunofluorescence.Serum IL-6 were quantitated using ELISA kits.The severity of pancreatitis and lung injury was determined by local pathological lesion(gross and histopathologie scoring).The lung tissure water content were detected,too.The effect of methylprednisolone were observed at the same time.
Results
1.The lung tissure water content increased at 6 hours after SAP model induction, and more at 12 hours(P＜0.05);higher than the control group(P＜0.01).
2.The Bmax of PMVECβ-AR decreased at 6 hours after SAP model induction, and more at 12 hours(P＜0.05);lower than the control group(P＜0.01).
3.The Kd value of PMVECβ-AR increased at 6 hours after SAP model induction, and more at 12 hours(P＜0.05);higher than the control group(P＜0.01).
4.The expression of GRK2 in lung increased at 6 hours after SAP model induction, and more at 12 hours(P＜0.05);higher than the control group(P＜0.01).
5.Intervention of methylprednisolone decreased water content,GRK2 expression, IL-6 in serum,Kd value of PMVECβ-AR and increased the Bmax of PMVECβ-AR(P＜0.05);and more at 12 hours(P＜0.05).
Conclusions
1.Lung injury occurs at 6 hours after SAP model induction in rats,and is more severe at 12 hours.
2.β-AR in pulmonary microvascular endothelial cells was lower down in severe acute pancreatitis-associated lung injury model in rats.
3.GRK2 expression in lung was higher up in severe acute pancreatitis-associated lung injury model in rats,and it maybe the mechanism of the decreasion ofβ-AR in pulmonary microvascular endothelial cells.
4.The intervention of methylprednisolone may attenuate the severity of acute pancreatitis-associated lung injury.
方法采用雄性SD大鼠,随机分设对照组、实验组和干预组。对照组剖腹后十二指肠翻动找到胰腺随即关腹;实验组予5%牛磺胆酸钠(1 ml/kg)逆行胰胆管注射,制备SAP模型;干预组在制模后30 min臀部肌肉注射甲强龙(30mg/kg)。观察制模后6h和12h的相关指标:胰腺和肺大体病理改变(肉眼观),胰腺和肺镜下病理改变(HE染色),肺组织含水量(干湿重法),肺微血管内皮细胞的β-AR的最大结合容量Bmax和平衡解离常数Kd(放射配基结合实验),肺组织GRK2表达(免疫荧光),血清IL-6水平变化(ELISA法)。
结果
1实验组肺组织含水量在制模后6h可见明显升高,12h更为明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
2.实验组β-AR最大结合容量Bmax在制模后6h可见明显降低,12h降低更为明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
3.实验组β-AR平衡解离常数Kd在制模后6h可见升高,12h更加明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
4.要验组肺组织GRK2表达在制模后6h即有升高,12h更加明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
5.实验组血清IL-6水平在制模后6h可见升高,12h更加明显(P＜0.05),与同时段对照组比较有显著性差异(P＜0.01)。
6.干预组与实验组比较:在6h,肺组织含水量减少,β-AR最大结合容量Bmax明显升高,β-AR平衡解离常数Kd可见降低,GRK2的表达显著降低,IL-6水平降低,有显著性差异(P＜0.05);在12h,各项指标变化更加明显,有显著性差异(P＜0.05)。
结论
1、SAP模型在制模后6h发现有肺损伤,12h更加严重。
2、SAP模型肺微血管内皮细胞的β-AR是下调的。
3、SAP模型肺组织GRK2表达显著增加,这可能是β-AR下调的重要机制,并与β-AR共同参与了SAP肺损伤的病理过程。
4、甲强龙可以上调β-AR,降低SAP模型肺组织GRK2表达,减轻肺水肿,改善肺内炎症反应,降低血清IL-6水平,减轻大鼠SAP肺损伤的严重程度,对SAP肺损伤具有保护作用。
Objective To investigate pathological changes,variation ofβ-AR in pulmonary microvascular endothelial cells and variation of GRK2 in lung and to explore the therapeutic effect of methyprednisolone in severe acute pancreatitis-associated lung injury model in rats.
Methods Male SD rats were divided into three groups randomly:the control group,the experimental group and the intervention group.In the control group, laparotomy were performed,duodenum and pancreas were flipped only.In the experimental group,acute necrotizing pancreatitis model was induced in rats by retrograde injection of 5%sodium taurocholate into biliopancreatic duct.In the intervention group,methylprednisolone(30mg/kg)was injected into rump musle of rats after models were developed.At 6 and 12 hours after model were developed, the maximum binding capacity(Bmax)and the Kd value of PMVECβ-AR was detected in lung by means of radioactive ligand binding assay.GRK2 expression was detected in lung by means of immunofluorescence.Serum IL-6 were quantitated using ELISA kits.The severity of pancreatitis and lung injury was determined by local pathological lesion(gross and histopathologie scoring).The lung tissure water content were detected,too.The effect of methylprednisolone were observed at the same time.
Results
1.The lung tissure water content increased at 6 hours after SAP model induction, and more at 12 hours(P＜0.05);higher than the control group(P＜0.01).
2.The Bmax of PMVECβ-AR decreased at 6 hours after SAP model induction, and more at 12 hours(P＜0.05);lower than the control group(P＜0.01).
3.The Kd value of PMVECβ-AR increased at 6 hours after SAP model induction, and more at 12 hours(P＜0.05);higher than the control group(P＜0.01).
4.The expression of GRK2 in lung increased at 6 hours after SAP model induction, and more at 12 hours(P＜0.05);higher than the control group(P＜0.01).
5.Intervention of methylprednisolone decreased water content,GRK2 expression, IL-6 in serum,Kd value of PMVECβ-AR and increased the Bmax of PMVECβ-AR(P＜0.05);and more at 12 hours(P＜0.05).
Conclusions
1.Lung injury occurs at 6 hours after SAP model induction in rats,and is more severe at 12 hours.
2.β-AR in pulmonary microvascular endothelial cells was lower down in severe acute pancreatitis-associated lung injury model in rats.
3.GRK2 expression in lung was higher up in severe acute pancreatitis-associated lung injury model in rats,and it maybe the mechanism of the decreasion ofβ-AR in pulmonary microvascular endothelial cells.
4.The intervention of methylprednisolone may attenuate the severity of acute pancreatitis-associated lung injury.
引文
1.Sekimoto M,Takada T,Kawarada Y,et al.JPN Guidelines for the management of acute pancreatitis:epidemiology,etiology,natural history,and outcome predictors in acute pancreatitis.JHBP Surg,2006,13:10-24.
2.肖贞良,孙耕耘,夏前明,等..肿瘤坏死因子致肺微血管内皮细胞单层通透性损伤的实验研究.中国应用生理学杂志,2001,17:79-81.
3.肖贞良,孙耕耘,黄碧琼,等.炎症损伤对肺微血管内皮细胞β-AR的影响.解放军医学杂志,2000,25:100-102.
4.Ferguson SS.Evolving concepts in G protein-coupled receptor endocytosis:the role in receptor desensitization and signaling.Pharmacol-Rev,2001:53:1-24.
5.陈紫薇,杨奎,下韵等.G蛋白偶联受体失敏及内吞相关蛋白的研究进展.生理科学进展,2001,34:55-58.
6.Pronin AN,Benovie J.Regulation of the G protein-coupled receptor kinase GRK5 by protein kinase C.J Biol Chem,1997,272:3806-3812.
7.Stephen S,G Ferguson.Evolving Concepts in G Protein-Coupled Receptor Endocytosis:The Role in Receptor Desensitization and Signaling.Pharmacological Reviews,2001,53:1-24.
8.Aho HA,Koskensalo ML,Nevalainen TJ.Experimental pancreatitis in the rat:Sodium taurocholate-induced acute haemorrhagie pancreatitis.Scand J Gastroenterol,1980,15:411-416.
9.Hughes CB,Grewal HP,Gaber LW,et al.Anti-TNFalpha therapy improves survival and ameliorates the pathophysiogic sequelae in acute pancreatitis in the rat.Am J of Surg,1996,171:274-280.
10.Schmidt J,Lewandrowski K,Warshaw AL,et al.Morphometric characteristics and homogeneity of a new model of acute pancreatitis in the rat.Int J Pancreatol,1992,12:41-51.
11.Hofbauer B,Saluja A K,Bhatia M,et al.Effect of recombinant platelet-activating factor acetylhydrolase on two models of experiment acute pancreatitis.Gastroenterology,1998,115:1238-1247.
12.Arthur EB.Mutiple Organ Failure,Mutiple Organ Dysfunction Syndrome and Systemic Inflammatory Response Syndrome.Arch Surg,1997,132:703-705.
13.周亚魁,吴云.急性胰腺炎鼠血液流变学与多器官损害的相关性.世界华人消化杂志,2000,8:1055-1057.
14.Folch E,Closa MD,Gelpi AE,et al.Effect of peritoneal lavage and lymph ligature on systemic complications of experimental acute pancreatitis.Dig Dis Sci,2000,45:909-914.
15.Zhang G,Zhang Z,Liu X.Intrapulmonary expression of tumor necrosis factor alpha mRNA and its significance in rats with acute pancreatitis.Huaxi Yike Daxue Xuebao,1999,30:379-383.
16.Peek GJ,White S,Scott AD.Severe acute respiratory distress syndrome secondary to acute pancreatitis successfully treated with extracorporeal membrance oxygenation in three patients.Ann Surg,1998,227:572-574.
17.张妞.急性坏死性胰腺炎的心肺损伤.国外医学外科学分册,1999,26:208-210.
18.Denham W,Yang J,Wang HC,et al.Inhibition of p38 mitogen activate kinase attenuate the svverity of pancreatitis-induced adult respriat(?)y distress syndrome.Crit Care Med,2000,28:2567-2572.
19.Gilgenast O,Brandt-Nedelev B,Wiswedel I,et al.Differential oxidative injury in extrapancreatie tissues during experimental pancreatitis:modification of lung proteins by 4-hydroxynonenal.Dig Dis Sci,2001,46:932-937.
20.Bhatia M,Saluja AK,Singh VP.Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury.Am J Physiol Gastrointest Liver Physiol,2001,280:974-978.
21.Kyriakides C,Jasleen J,Wang Y,et al.Neutrophils not complement,mediate the mortality of experimental hemorrhagic pancreatitis.Pancreas,2001,22:40-46.
22.黄筵庭.重症胰腺炎的手术适应征和手术时机问题.临床外科杂志,1995,3:172-173.
23.中华医学会外科学胰腺分组,急性胰腺炎的临床诊断与分级标准.中华外科杂志,1997,35:773-776.
24.陈帆,贺军,袁春.重症胰腺炎与多器官衰竭动物模型.中华实验外科杂志,1991,8:24.
25.Willemer S,et al.Lung injury in acute experimental pancreatitis in rats.Int J Pancreatol,1991,8:305.
26.张延龄.急性胰腺炎的实验模型.国外医学外科学分册,1995,22:68.
27.姜永锋.急性胰腺炎的实验研究进展.国外医学外科学分册,1996,23:13.
28.Michael L,Steer.Relationship between pancreatitic and lung injujry.Respiration Physiology,2001,128:13-16.
29.Norman JG,Franz MG,Fink GS,et al.Decreased mortality of severe acute pancreatitis after proximal cytokine eblockade.Ann Surg,1995,221:625-631.
30.Tenner S,Banks PA.Acute pancreatitis:non surgical management.World J Surg,1997,21:143-148.
31.Saluja AK,Steer MLP6.Pathophysiology of pancreatitis:Role of cytokines and other mediators of inflammation.Digestion,1999,60:27-33.
32.McKay CJ,Buter A.Natural history of organ failure in acute pancreatitis.Pancreatology.2008,3:111-114.
33.Hiithofer K,Gastillo CFD,Fridh TW,et al.Increased induxed experimental pancreatitis.Ann Surg,1995,211:364-371.
34.王自法,潘承恩,刘绍诰.急性胰腺炎中炎症介质的作用.华人消化杂志,1998,7:170-171.
35.Zhao X,Andesson R,Wang X,et al.Acute pancreatitis-associated lung injury:pathophysiologica(?)mechanisms and potentiai future therapies.Scana J Gastroenterol,2002,37:1351-1358.
36.Stefanie H,Frank L,Stefanie E,et al.Insulin-like growth factor-1-media-ted neuroprotection against Oxidative stress is associated with activation of nuclear factor kB.The Journal of Biological Chemistry,1999,274:9828-9835.
37.Urunuela A,Sevillano S,de la Mano AM.Time-course of oxygen free radical production in acinar cells during acute pancreatitis induced by pancreatic duct obstruction.Biochim Biophys Acta,2002 Nov 20,1588:159-64.
38.Carstairs JR.Autoradiographic visualization of beta-adrenoceptor subtype in human lung.Am Rev Respir Dis,1985,132:541.
39.Tota MR,Candelor MR,Dixan RAF,et al.Biophysical and genetic analysis of the ligand-binding of the β-adrenoceptor.Trend Pharmacol Sci,1991,12:4-6.
40.Steinberg SF,Jaffe EA,Bilezikian JP,et al.Endothelial cells contain beta adrenoceptors.Naunyn-Schmiedeberg's Arch Pharmacol,1984,325:310-313.
41.Graf K,Grafe M,Dummler U,et al.Regulation ofβ-adrenergic receptors on endothelial cells in culture.Eur Heart J,1993,14:173-176.
42.Das SK,Mukherjee S,Bannerjee DK.β-Adrenoceptors of multiple affinities in a clonal capillay endothelial cell line and its functional implication.Mol and Cell Biochem,1994,140:49-54.
43.Hausdorff WP,Caron MG,Lefkowitz RJ.Turning off the signal:desensitization of beta-adrenergic receptor function.FASEB J,1990,4:2881-2889.
44.Palczewski K,Benovic JL.G protein-coupled receptor kinases.Trends Biochem Sci,1991,16:387-391.
45.Premont RT,Inglese J,Lefkowitz RJ.Protei(?)ki(?)as(?)that.phosphorylate activated G protein-coupled receptors.FASEB J,1995,9:175-182.
46.Weiss ER,Ducceschi MH,Homer TJ,et al.Species-specific differences in expression of G-protein-coupled receptor kinase(GRK)7 and GRK1 in mammalian cone photoreceptor cells:implications for cone cell phototransduction.J Neuro Sci,2001,21:9175-84.
47.Opperman M,Diverse-Pierluissi M,Drazner MH,et al.Mono(?)lonal antibodiesr eveal receptor specificity among G-protein-coupled receptor kinases.Proc Natl Acad Sci USA,1996,93:7649-7654.
48.Benovic JL,Strasser RH,Caron MG,et al.β-adrenergic receptor kinase:identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor.Pro Natl Acad Sci USA,1986,83:2797-801.
49.Benovic JL,Mayor F Jr,Staniszewiski C,et al.Purification and characterization of the beta-adrenergic receptor kinase.J Biol Chem,1987,262:9026-9032.
50.Benovic JL,DeBlasi A,Stone WC,et al.Beta-adrenergic receptor kinase:primary structure delineates a multigene family.Science,1989,246:235-240.
51.Benovic JL,Stone WC,Huebner K,et al.cDNA cloning and chromosomal localization of the humana-adrenergic receptor kinase.FEBS,1991,283:122-126.
52.Krupnick JG,Benovic JL.The role of receptor kinases and arrestins in G protein-coupled receptor regulation.Ann Rev Pharmacol Toxicol,1998,38:238-319.
53.Penn RB,Pronin AN,Benovic JL.Regulation of G protein-coupled receptor kinases.Trends Cardiovasc Med,2000,10:81-89.
54.Theilade J,Haunso S,Sheikh SP.G protein-coupled receptor kinase 2-a feedback regulator of Gq pathway signaling.Curr Drug Targets Immune Endocr Metabol Disord,2001,1:139-51.
55.Mekay CJ,Gallagher G.Brooks B,et al.Increased monoeyte cytokine production in association with systemi(?)complications in acute pan(?)titis.British Journal of Surgery,1996,83:919-923.
56.王自法,潘承恩,刘绍诰,等.地塞米松抑制炎症介质改善大鼠重症急性胰腺炎的预后.中华肝胆外科杂志,2001,7:181-182.
57.董瑞,王自法,吕毅,等.大剂量地塞米松治疗重症急性胰腺炎的实验研究.中国普通外科杂志,2001,10:309-312.
58.Osman MO,Jacobsen NO,Kristensen JU,et al.Beneficial effects of hydrocortisone in a model of experimental acute pancreatitis.Digestiev Surgery,1999,16:214-221.
59.Kataoka K,Sakagami J.The effect of steroid pulse therapy on the development of a cute pancreatitis induced by dosed duodenal loop in rats.Gastroenterol,2002,37:537-542.
1.Wess J.G-protein-coupled receptors:molecular mechanisms involved in receptor activation and selectivity of G-protein recognition.FASEB J,1997,11:346-354.
2.Ji TH,Grossmann M,Ji I.G Protein-coupled receptors I Diversity of receptor-ligand interactions.J Biol Chem,1998,273:17299-17302.
3.Bargmann CI.The mechanism of anesthetic activatiom of TREK-1 and TASK was proved by using genetic constructs as well as by recording from excised patches.Science,1998,282:2028-2033.
4.Venter JC,Adams MD,Myers EW,et al.The Sequence of the Human Genome.Science,2001,291:1304-1351.
5.Ferguson SS.Evolving concepts in G protein-coupled receptor endocytosis:the role in receptor desensitization and signaling.Pharmacol-Rev.2001,53(1):1-24.
6.Dohlman HG,Thomer J,Caron MG,et al.Model system for the study of aeven-transmembrane-segment receptor.Annu Rev Biochem,1991,60:653-688.
7.Pronin AN,Benovic J.Regulation of the G protein-coupled receptor kinase GRK5 by protein kinase C.J Biological Chem,1997,272(6):3806-3812.
8.Stephen S.G Ferguson.Evolving Concepts in G Protein-Coupled Receptor Endocytosis:The Role in Receptor Desensitization and Signaling.Pharmacological Reviews,2001,53(1):1-24.
9.Wess J.G-protein-coupled receptors:molecular mechanisms involved in receptor activation and selectivity of G-protein recognition.FASEB J,1997,11:346-354.
10.Hausdorff WP,Caron MG,Lefkowitz RJ.Turning off the signal:desensitization of beta-adrenergie receptor function.FASEB J,1990,4:2881-2889.
11.Palczewski K,Benovie JL.G.protein-coupled receptor kinase.Trends Biochem Sci,1991,16:387-391.
12.Cong M,Perry SJ,Lin FT,et.al.Regulation of membrance targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79.J Biol Chem,2001,276(18):15192-15199.
13.Krasel C,Dammeier S,Winstel R,et al.Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin,J Biol Chem,2001,276(3):1911-5.
14.Palczewski K,Benovic JL.G protein-coupled receptor kinase.Trends Biochem Sci,1991,16:387-391.
15.Pitcher JA,Freedman N J,Lefkowitz RJ.G protein-coupled receptor kinases.Ann R(?)v Biochem,1998,67:653-692.
16.Rapaceiuolo A,Suvarna S,Barki-Harrington L,et al.Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathways.J Biol Chem,2003,278:35403-35411.
17.Ji TH,Grcssmann M,Ji I,et al.G protein-coupled receptors.J Biol Chem,1998,273(20)17299-17302.
18.Premont RT,Inglese J,Lefkowitz RJ.Protein kinases that phosphorylate activated G protein-coupled receptors.FASEB J,1995,9:175-182.
19.Weiss ER.The cloning of GRK7,a candidate cone opsin kinase,from cone and rod-dominant mammalian retinas.Mol Vis,1998,4:27.
20.Fredriksson R,Hoglund PJ,Gloriam DE,et al.Seven evolutionarilv conserved human rhodopsin G protein-coupled receptors lacking close relatives.FEBS Lett,2003,554:381-388.
21.Chen CK,Zhang K,Church-Kopish J,et al.Characterization of human GRK7as a potential cone opsin kinase.Mol Vis,2001,7:305-313.
22.Benovic JL,Strasser RH,Caron MG,et al.Beta-adrenergic receptor kinase:identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor.Proc Natl Acad Sci USA,1986,83:2797-2801.
23.Oppermann M,Diverse-Pierluissi M,Drazner MH,et al.Monoelonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases.Proc Natl Acad Sci USA,1996,93:7469-7654.
24.Pitcher JA,Inglese J,Higg JB,et al.Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrance-bound receptors.Science,1992,257:1264-1267.
25.Pitcher JA,Touhara K,Payne ES,et al.Pleckstrirn homology domain-mediated membrance association and activation of the beta-adrenergic receptor kinase requires coordinate interaction with G beta gamma subunits and lipid.J Biol Chem,1995,270:11707-11710.
26.H(?)nes KD,Babwah AV,Dale IR et al Differential regulation of corticotrophin releasing factor lalpha receptor endocytosis and trafficking by beta-arrestins.and Rab GTPases.J Neurochem,2006,96:934-949.
27.Gainetdinov RR,Premont RT,Caron MG,et al.Reply:receptor specificity of G protein-coupled receptor kinases.Trends Pharmacol Sci,2000,21:366-367.
28.Penn RB,Pronin AN,Benovic JL.Regulation of G protein-coupled receptor kinases.Trends Cardiovasc Med,2000,10:81-89.
29.Premont RT.Once and future signaling:G protein-coupled receptor kinase control of neuronal sensitivity.Neuromolecular Med,2005,7:129-147.
30.Ohguro H,Palczewski K,Ericsson LH,et al.Sequential phosphorylation of rhodopsin at multiple sites.Biochemistry,1993,32:5718-5724.
31.Gan X,Ma Z,Deng N,et al.Involvement of the C-terminal praline-rich motif of G protein-coupled receptor kinases in recognition of activated rhodopsin.J Biol Chem,2004,279:49741-49746.
32.Freeman JL,Pollard TD,Lefkowitz RJ.Regulation of GRKS by actin.J Biol Chem,1998,273(32):20653-20657.
33.Clapham DE,Neer EJ.G protein βγ subunits.Annu Rev Pharmaol Toxicol,1997,37:167-203.
34.Eichmann T,Lorenz K,Hoffman M,et al.The aminoterminal domain of G protein-coupled receptor kinase 2 is a regulatory G beta gamma binding site.J Biol Chem,2003,278:8052-8057.
35.Dhami GK,Dale LB,Anborgh PH,et al.G protein-coupled receptor kinase 2regulator of G protein signaling homology domain binds to both metabotropic glutamate receptor la and Galphaq to attenuate signaling.J Biof Chem,2004,279:16614-16620.
36.Winstel R,Frend S,Krasel C,et al.Protein kinase cross-talk:membrance targeting of the beta-adrenergic receptor kinase by protein kinase C.Proc Natl Acad Sci USA,1996,93:2105-2109.
37.Krasel C,Dammeier S,Winstel R,et al.Phosphorylation of GRK2 by protein kin(?)se C abolishes(?)inhibition by calmodu(?)J Biol Chem,2001,276:1911-1915.
38.Lee JH,Jeong SM,Lee BH,et al.Prevention of ginsenoside-induced desensitization of Ca~(2+)-activated Cl-current by microiniection of inositol hexakisphosphate in Xenopus laevis oocytes:involvement of GRK2 and beta-arrestin I.J Biol Chem,2004,279:9912-9921.
39.Rockman HA,Choi DJ,Rahman NU,et al.Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase 5 in transgenic mice.Proc Natl Acad Sci USA,1996,93:9954-9959.
40.Gray JA,Sheffler DJ,Bhatnagar A,et al.Cell-type specific effects of endocytosis inhibitors on 5-hydroxytryptamine(2A)receptor desensitization and resensitization reveal an arrestin,GRK2,and GRK5 independent mode of regulation in human embryonic kidney 293 cells.Mol Pharmacol,2001,60:1020-1030.
41.Freeman JL,Pitcher JA,Li X.Alpha-actinin is a potent regulator of GRKs activity and substrate specificity in vitro.FEBS Lett,2000,473(3):280-284.
42.Pronin AN,Satpaer DK,Slepak RZ.Regulation of GRKs by calmodulin and localization of the calmodulin binging domaln.J Biol Chem,1997,272:18273-18280.
43.Iacovelli L,Sallese M,Blasi AD.Regulation of GRK subunits by calcium sensor protein.FASEB,1999,131(1):1-8.
44.Sakmar TP.Rhodopsin:A prototypical G protein-coupled receptor.Prog Nucleic Acid Res Mol Biol,1998,59:1-34.
45.Siderovski DP,Stroekbine B,Behe CI.Whither goest the RGS proteins? Crit Rev Biochem Mol Biol,1999,34:215-251.
46.Iacovelli L,Sallese M,Mariggio S,et al.Regulation of G-protein-coupled receptor kinase subtypes by calcium sensor proteins.FASEB J,1999,13:1-8.
47.Touhara K,Inglese J,Pitcher JA,et al.Binding of G protein-subunits to plecstrin homology domains.J Biol Chem,1994,269:10217-10220.
48.Di(?)ker Quitterer U,Winstel R,et al.Phosph(?)rylstion-ind(?)pendent inhibition of parathyroid hormone receptor signaling by G protein-coupled receptor kinases.Proc Natl Acad Sci USA,1999,96:5476-5481.
49.Elorza A,Samago S,Mayor F.Agonist-dependent modulation of G proteincoupled receptor kinase 2 by mitogen-activated protein kinases.Mol Pharmacol,2000,57:778-783.
50.Sarnago S,Elorza A,Mayor F.Agonist-dependent phosphorylation of the G protein-coupled receptor kinase 2(GRK2)by Src tyrosine kinase.Biol Chem,1999,274:34411-34416.
51.Stoffel RH,Inglese J,Macrae AD,et al.Palmitoylation increases the kinase activity of the G protein-coupled receptor kinase,GRK6.Biochemistry,1998,37:16053-16059.
52.Premont RT,Koch WJ,Inglese J,et al.Identification,purification,and characterization of GRK5,a member of the family of G protein-coupled receptor kinases.Biol Chem,1994,269:6832-6841.
53.Kunapuli P,Gurevieh VV,Benovic JL.Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRKS.J Biol Chem,1994,269:10209-10212.
54.Chuang DM,Costa E.Evidence for internalization of the recognition site of β-adrenergie receptors during receptor subsensitivity induced by isoproterenol.Proc Natl Acad Sci USA,1979,76:3024-3028.
55.Staehelin M,Simons P.Rapid and reversible disappearance of β-adrenergic cell surface receptors.EMBO J,1982,1:187-190.
56.Barak LS,Ferguson SSG,Zhang J,et al.Internal trafficking and surface mobility of a functionally intact 2-adrenergie receptor-green fluorescent protein conjugate.Mol Pharmacol,1997a,51:177-184.
57.Ferguson G,Watterson KR,Palmer TM.Subtype-specific kinetics of inhibitory adenosine receptor intemalization are determined by sensitivity to phosphorylation by G protein-coupled receptor kinases.Mol Pharmacol,2000,57:546-552.
58.Hausd(?)ff WP Bouvier M,O'Dowd RF,et al.(?)phorylation sites(?)two domains of the 2-adrenergic receptor are involved in distinct pathways of receptor desensitization.J Biol Chem,1989,264:12657-1266.
59.Moro O,Lameh J,Sadee W.Serine-and threonine-rich domain regulates internalization of muscarinic cholinergic receptors.J Biol Chem,1993,268:6862-6865
60.Tsuga(?),Kameyama K,Haga T,et al.Sequesuation of muscarinic acet(?)choline receptor m2 subtypes:Facilitation by G protein-coupled receptor kinase(GRK2)and attenuation by a dominant-negative mutant of GRK2.J Biol Chem,1994,269:32522-32527.
61.Barlic J,Khandaker LS,Mahon MH,et al.β-Arresfins regulate interleukin-8(IL-8)-induced CXCR1 internalization.J Biol Chem,1999,274:16287-16294.
2.肖贞良,孙耕耘,夏前明,等..肿瘤坏死因子致肺微血管内皮细胞单层通透性损伤的实验研究.中国应用生理学杂志,2001,17:79-81.
3.肖贞良,孙耕耘,黄碧琼,等.炎症损伤对肺微血管内皮细胞β-AR的影响.解放军医学杂志,2000,25:100-102.
4.Ferguson SS.Evolving concepts in G protein-coupled receptor endocytosis:the role in receptor desensitization and signaling.Pharmacol-Rev,2001:53:1-24.
5.陈紫薇,杨奎,下韵等.G蛋白偶联受体失敏及内吞相关蛋白的研究进展.生理科学进展,2001,34:55-58.
6.Pronin AN,Benovie J.Regulation of the G protein-coupled receptor kinase GRK5 by protein kinase C.J Biol Chem,1997,272:3806-3812.
7.Stephen S,G Ferguson.Evolving Concepts in G Protein-Coupled Receptor Endocytosis:The Role in Receptor Desensitization and Signaling.Pharmacological Reviews,2001,53:1-24.
8.Aho HA,Koskensalo ML,Nevalainen TJ.Experimental pancreatitis in the rat:Sodium taurocholate-induced acute haemorrhagie pancreatitis.Scand J Gastroenterol,1980,15:411-416.
9.Hughes CB,Grewal HP,Gaber LW,et al.Anti-TNFalpha therapy improves survival and ameliorates the pathophysiogic sequelae in acute pancreatitis in the rat.Am J of Surg,1996,171:274-280.
10.Schmidt J,Lewandrowski K,Warshaw AL,et al.Morphometric characteristics and homogeneity of a new model of acute pancreatitis in the rat.Int J Pancreatol,1992,12:41-51.
11.Hofbauer B,Saluja A K,Bhatia M,et al.Effect of recombinant platelet-activating factor acetylhydrolase on two models of experiment acute pancreatitis.Gastroenterology,1998,115:1238-1247.
12.Arthur EB.Mutiple Organ Failure,Mutiple Organ Dysfunction Syndrome and Systemic Inflammatory Response Syndrome.Arch Surg,1997,132:703-705.
13.周亚魁,吴云.急性胰腺炎鼠血液流变学与多器官损害的相关性.世界华人消化杂志,2000,8:1055-1057.
14.Folch E,Closa MD,Gelpi AE,et al.Effect of peritoneal lavage and lymph ligature on systemic complications of experimental acute pancreatitis.Dig Dis Sci,2000,45:909-914.
15.Zhang G,Zhang Z,Liu X.Intrapulmonary expression of tumor necrosis factor alpha mRNA and its significance in rats with acute pancreatitis.Huaxi Yike Daxue Xuebao,1999,30:379-383.
16.Peek GJ,White S,Scott AD.Severe acute respiratory distress syndrome secondary to acute pancreatitis successfully treated with extracorporeal membrance oxygenation in three patients.Ann Surg,1998,227:572-574.
17.张妞.急性坏死性胰腺炎的心肺损伤.国外医学外科学分册,1999,26:208-210.
18.Denham W,Yang J,Wang HC,et al.Inhibition of p38 mitogen activate kinase attenuate the svverity of pancreatitis-induced adult respriat(?)y distress syndrome.Crit Care Med,2000,28:2567-2572.
19.Gilgenast O,Brandt-Nedelev B,Wiswedel I,et al.Differential oxidative injury in extrapancreatie tissues during experimental pancreatitis:modification of lung proteins by 4-hydroxynonenal.Dig Dis Sci,2001,46:932-937.
20.Bhatia M,Saluja AK,Singh VP.Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury.Am J Physiol Gastrointest Liver Physiol,2001,280:974-978.
21.Kyriakides C,Jasleen J,Wang Y,et al.Neutrophils not complement,mediate the mortality of experimental hemorrhagic pancreatitis.Pancreas,2001,22:40-46.
22.黄筵庭.重症胰腺炎的手术适应征和手术时机问题.临床外科杂志,1995,3:172-173.
23.中华医学会外科学胰腺分组,急性胰腺炎的临床诊断与分级标准.中华外科杂志,1997,35:773-776.
24.陈帆,贺军,袁春.重症胰腺炎与多器官衰竭动物模型.中华实验外科杂志,1991,8:24.
25.Willemer S,et al.Lung injury in acute experimental pancreatitis in rats.Int J Pancreatol,1991,8:305.
26.张延龄.急性胰腺炎的实验模型.国外医学外科学分册,1995,22:68.
27.姜永锋.急性胰腺炎的实验研究进展.国外医学外科学分册,1996,23:13.
28.Michael L,Steer.Relationship between pancreatitic and lung injujry.Respiration Physiology,2001,128:13-16.
29.Norman JG,Franz MG,Fink GS,et al.Decreased mortality of severe acute pancreatitis after proximal cytokine eblockade.Ann Surg,1995,221:625-631.
30.Tenner S,Banks PA.Acute pancreatitis:non surgical management.World J Surg,1997,21:143-148.
31.Saluja AK,Steer MLP6.Pathophysiology of pancreatitis:Role of cytokines and other mediators of inflammation.Digestion,1999,60:27-33.
32.McKay CJ,Buter A.Natural history of organ failure in acute pancreatitis.Pancreatology.2008,3:111-114.
33.Hiithofer K,Gastillo CFD,Fridh TW,et al.Increased induxed experimental pancreatitis.Ann Surg,1995,211:364-371.
34.王自法,潘承恩,刘绍诰.急性胰腺炎中炎症介质的作用.华人消化杂志,1998,7:170-171.
35.Zhao X,Andesson R,Wang X,et al.Acute pancreatitis-associated lung injury:pathophysiologica(?)mechanisms and potentiai future therapies.Scana J Gastroenterol,2002,37:1351-1358.
36.Stefanie H,Frank L,Stefanie E,et al.Insulin-like growth factor-1-media-ted neuroprotection against Oxidative stress is associated with activation of nuclear factor kB.The Journal of Biological Chemistry,1999,274:9828-9835.
37.Urunuela A,Sevillano S,de la Mano AM.Time-course of oxygen free radical production in acinar cells during acute pancreatitis induced by pancreatic duct obstruction.Biochim Biophys Acta,2002 Nov 20,1588:159-64.
38.Carstairs JR.Autoradiographic visualization of beta-adrenoceptor subtype in human lung.Am Rev Respir Dis,1985,132:541.
39.Tota MR,Candelor MR,Dixan RAF,et al.Biophysical and genetic analysis of the ligand-binding of the β-adrenoceptor.Trend Pharmacol Sci,1991,12:4-6.
40.Steinberg SF,Jaffe EA,Bilezikian JP,et al.Endothelial cells contain beta adrenoceptors.Naunyn-Schmiedeberg's Arch Pharmacol,1984,325:310-313.
41.Graf K,Grafe M,Dummler U,et al.Regulation ofβ-adrenergic receptors on endothelial cells in culture.Eur Heart J,1993,14:173-176.
42.Das SK,Mukherjee S,Bannerjee DK.β-Adrenoceptors of multiple affinities in a clonal capillay endothelial cell line and its functional implication.Mol and Cell Biochem,1994,140:49-54.
43.Hausdorff WP,Caron MG,Lefkowitz RJ.Turning off the signal:desensitization of beta-adrenergic receptor function.FASEB J,1990,4:2881-2889.
44.Palczewski K,Benovic JL.G protein-coupled receptor kinases.Trends Biochem Sci,1991,16:387-391.
45.Premont RT,Inglese J,Lefkowitz RJ.Protei(?)ki(?)as(?)that.phosphorylate activated G protein-coupled receptors.FASEB J,1995,9:175-182.
46.Weiss ER,Ducceschi MH,Homer TJ,et al.Species-specific differences in expression of G-protein-coupled receptor kinase(GRK)7 and GRK1 in mammalian cone photoreceptor cells:implications for cone cell phototransduction.J Neuro Sci,2001,21:9175-84.
47.Opperman M,Diverse-Pierluissi M,Drazner MH,et al.Mono(?)lonal antibodiesr eveal receptor specificity among G-protein-coupled receptor kinases.Proc Natl Acad Sci USA,1996,93:7649-7654.
48.Benovic JL,Strasser RH,Caron MG,et al.β-adrenergic receptor kinase:identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor.Pro Natl Acad Sci USA,1986,83:2797-801.
49.Benovic JL,Mayor F Jr,Staniszewiski C,et al.Purification and characterization of the beta-adrenergic receptor kinase.J Biol Chem,1987,262:9026-9032.
50.Benovic JL,DeBlasi A,Stone WC,et al.Beta-adrenergic receptor kinase:primary structure delineates a multigene family.Science,1989,246:235-240.
51.Benovic JL,Stone WC,Huebner K,et al.cDNA cloning and chromosomal localization of the humana-adrenergic receptor kinase.FEBS,1991,283:122-126.
52.Krupnick JG,Benovic JL.The role of receptor kinases and arrestins in G protein-coupled receptor regulation.Ann Rev Pharmacol Toxicol,1998,38:238-319.
53.Penn RB,Pronin AN,Benovic JL.Regulation of G protein-coupled receptor kinases.Trends Cardiovasc Med,2000,10:81-89.
54.Theilade J,Haunso S,Sheikh SP.G protein-coupled receptor kinase 2-a feedback regulator of Gq pathway signaling.Curr Drug Targets Immune Endocr Metabol Disord,2001,1:139-51.
55.Mekay CJ,Gallagher G.Brooks B,et al.Increased monoeyte cytokine production in association with systemi(?)complications in acute pan(?)titis.British Journal of Surgery,1996,83:919-923.
56.王自法,潘承恩,刘绍诰,等.地塞米松抑制炎症介质改善大鼠重症急性胰腺炎的预后.中华肝胆外科杂志,2001,7:181-182.
57.董瑞,王自法,吕毅,等.大剂量地塞米松治疗重症急性胰腺炎的实验研究.中国普通外科杂志,2001,10:309-312.
58.Osman MO,Jacobsen NO,Kristensen JU,et al.Beneficial effects of hydrocortisone in a model of experimental acute pancreatitis.Digestiev Surgery,1999,16:214-221.
59.Kataoka K,Sakagami J.The effect of steroid pulse therapy on the development of a cute pancreatitis induced by dosed duodenal loop in rats.Gastroenterol,2002,37:537-542.
1.Wess J.G-protein-coupled receptors:molecular mechanisms involved in receptor activation and selectivity of G-protein recognition.FASEB J,1997,11:346-354.
2.Ji TH,Grossmann M,Ji I.G Protein-coupled receptors I Diversity of receptor-ligand interactions.J Biol Chem,1998,273:17299-17302.
3.Bargmann CI.The mechanism of anesthetic activatiom of TREK-1 and TASK was proved by using genetic constructs as well as by recording from excised patches.Science,1998,282:2028-2033.
4.Venter JC,Adams MD,Myers EW,et al.The Sequence of the Human Genome.Science,2001,291:1304-1351.
5.Ferguson SS.Evolving concepts in G protein-coupled receptor endocytosis:the role in receptor desensitization and signaling.Pharmacol-Rev.2001,53(1):1-24.
6.Dohlman HG,Thomer J,Caron MG,et al.Model system for the study of aeven-transmembrane-segment receptor.Annu Rev Biochem,1991,60:653-688.
7.Pronin AN,Benovic J.Regulation of the G protein-coupled receptor kinase GRK5 by protein kinase C.J Biological Chem,1997,272(6):3806-3812.
8.Stephen S.G Ferguson.Evolving Concepts in G Protein-Coupled Receptor Endocytosis:The Role in Receptor Desensitization and Signaling.Pharmacological Reviews,2001,53(1):1-24.
9.Wess J.G-protein-coupled receptors:molecular mechanisms involved in receptor activation and selectivity of G-protein recognition.FASEB J,1997,11:346-354.
10.Hausdorff WP,Caron MG,Lefkowitz RJ.Turning off the signal:desensitization of beta-adrenergie receptor function.FASEB J,1990,4:2881-2889.
11.Palczewski K,Benovie JL.G.protein-coupled receptor kinase.Trends Biochem Sci,1991,16:387-391.
12.Cong M,Perry SJ,Lin FT,et.al.Regulation of membrance targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79.J Biol Chem,2001,276(18):15192-15199.
13.Krasel C,Dammeier S,Winstel R,et al.Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin,J Biol Chem,2001,276(3):1911-5.
14.Palczewski K,Benovic JL.G protein-coupled receptor kinase.Trends Biochem Sci,1991,16:387-391.
15.Pitcher JA,Freedman N J,Lefkowitz RJ.G protein-coupled receptor kinases.Ann R(?)v Biochem,1998,67:653-692.
16.Rapaceiuolo A,Suvarna S,Barki-Harrington L,et al.Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathways.J Biol Chem,2003,278:35403-35411.
17.Ji TH,Grcssmann M,Ji I,et al.G protein-coupled receptors.J Biol Chem,1998,273(20)17299-17302.
18.Premont RT,Inglese J,Lefkowitz RJ.Protein kinases that phosphorylate activated G protein-coupled receptors.FASEB J,1995,9:175-182.
19.Weiss ER.The cloning of GRK7,a candidate cone opsin kinase,from cone and rod-dominant mammalian retinas.Mol Vis,1998,4:27.
20.Fredriksson R,Hoglund PJ,Gloriam DE,et al.Seven evolutionarilv conserved human rhodopsin G protein-coupled receptors lacking close relatives.FEBS Lett,2003,554:381-388.
21.Chen CK,Zhang K,Church-Kopish J,et al.Characterization of human GRK7as a potential cone opsin kinase.Mol Vis,2001,7:305-313.
22.Benovic JL,Strasser RH,Caron MG,et al.Beta-adrenergic receptor kinase:identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor.Proc Natl Acad Sci USA,1986,83:2797-2801.
23.Oppermann M,Diverse-Pierluissi M,Drazner MH,et al.Monoelonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases.Proc Natl Acad Sci USA,1996,93:7469-7654.
24.Pitcher JA,Inglese J,Higg JB,et al.Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrance-bound receptors.Science,1992,257:1264-1267.
25.Pitcher JA,Touhara K,Payne ES,et al.Pleckstrirn homology domain-mediated membrance association and activation of the beta-adrenergic receptor kinase requires coordinate interaction with G beta gamma subunits and lipid.J Biol Chem,1995,270:11707-11710.
26.H(?)nes KD,Babwah AV,Dale IR et al Differential regulation of corticotrophin releasing factor lalpha receptor endocytosis and trafficking by beta-arrestins.and Rab GTPases.J Neurochem,2006,96:934-949.
27.Gainetdinov RR,Premont RT,Caron MG,et al.Reply:receptor specificity of G protein-coupled receptor kinases.Trends Pharmacol Sci,2000,21:366-367.
28.Penn RB,Pronin AN,Benovic JL.Regulation of G protein-coupled receptor kinases.Trends Cardiovasc Med,2000,10:81-89.
29.Premont RT.Once and future signaling:G protein-coupled receptor kinase control of neuronal sensitivity.Neuromolecular Med,2005,7:129-147.
30.Ohguro H,Palczewski K,Ericsson LH,et al.Sequential phosphorylation of rhodopsin at multiple sites.Biochemistry,1993,32:5718-5724.
31.Gan X,Ma Z,Deng N,et al.Involvement of the C-terminal praline-rich motif of G protein-coupled receptor kinases in recognition of activated rhodopsin.J Biol Chem,2004,279:49741-49746.
32.Freeman JL,Pollard TD,Lefkowitz RJ.Regulation of GRKS by actin.J Biol Chem,1998,273(32):20653-20657.
33.Clapham DE,Neer EJ.G protein βγ subunits.Annu Rev Pharmaol Toxicol,1997,37:167-203.
34.Eichmann T,Lorenz K,Hoffman M,et al.The aminoterminal domain of G protein-coupled receptor kinase 2 is a regulatory G beta gamma binding site.J Biol Chem,2003,278:8052-8057.
35.Dhami GK,Dale LB,Anborgh PH,et al.G protein-coupled receptor kinase 2regulator of G protein signaling homology domain binds to both metabotropic glutamate receptor la and Galphaq to attenuate signaling.J Biof Chem,2004,279:16614-16620.
36.Winstel R,Frend S,Krasel C,et al.Protein kinase cross-talk:membrance targeting of the beta-adrenergic receptor kinase by protein kinase C.Proc Natl Acad Sci USA,1996,93:2105-2109.
37.Krasel C,Dammeier S,Winstel R,et al.Phosphorylation of GRK2 by protein kin(?)se C abolishes(?)inhibition by calmodu(?)J Biol Chem,2001,276:1911-1915.
38.Lee JH,Jeong SM,Lee BH,et al.Prevention of ginsenoside-induced desensitization of Ca~(2+)-activated Cl-current by microiniection of inositol hexakisphosphate in Xenopus laevis oocytes:involvement of GRK2 and beta-arrestin I.J Biol Chem,2004,279:9912-9921.
39.Rockman HA,Choi DJ,Rahman NU,et al.Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase 5 in transgenic mice.Proc Natl Acad Sci USA,1996,93:9954-9959.
40.Gray JA,Sheffler DJ,Bhatnagar A,et al.Cell-type specific effects of endocytosis inhibitors on 5-hydroxytryptamine(2A)receptor desensitization and resensitization reveal an arrestin,GRK2,and GRK5 independent mode of regulation in human embryonic kidney 293 cells.Mol Pharmacol,2001,60:1020-1030.
41.Freeman JL,Pitcher JA,Li X.Alpha-actinin is a potent regulator of GRKs activity and substrate specificity in vitro.FEBS Lett,2000,473(3):280-284.
42.Pronin AN,Satpaer DK,Slepak RZ.Regulation of GRKs by calmodulin and localization of the calmodulin binging domaln.J Biol Chem,1997,272:18273-18280.
43.Iacovelli L,Sallese M,Blasi AD.Regulation of GRK subunits by calcium sensor protein.FASEB,1999,131(1):1-8.
44.Sakmar TP.Rhodopsin:A prototypical G protein-coupled receptor.Prog Nucleic Acid Res Mol Biol,1998,59:1-34.
45.Siderovski DP,Stroekbine B,Behe CI.Whither goest the RGS proteins? Crit Rev Biochem Mol Biol,1999,34:215-251.
46.Iacovelli L,Sallese M,Mariggio S,et al.Regulation of G-protein-coupled receptor kinase subtypes by calcium sensor proteins.FASEB J,1999,13:1-8.
47.Touhara K,Inglese J,Pitcher JA,et al.Binding of G protein-subunits to plecstrin homology domains.J Biol Chem,1994,269:10217-10220.
48.Di(?)ker Quitterer U,Winstel R,et al.Phosph(?)rylstion-ind(?)pendent inhibition of parathyroid hormone receptor signaling by G protein-coupled receptor kinases.Proc Natl Acad Sci USA,1999,96:5476-5481.
49.Elorza A,Samago S,Mayor F.Agonist-dependent modulation of G proteincoupled receptor kinase 2 by mitogen-activated protein kinases.Mol Pharmacol,2000,57:778-783.
50.Sarnago S,Elorza A,Mayor F.Agonist-dependent phosphorylation of the G protein-coupled receptor kinase 2(GRK2)by Src tyrosine kinase.Biol Chem,1999,274:34411-34416.
51.Stoffel RH,Inglese J,Macrae AD,et al.Palmitoylation increases the kinase activity of the G protein-coupled receptor kinase,GRK6.Biochemistry,1998,37:16053-16059.
52.Premont RT,Koch WJ,Inglese J,et al.Identification,purification,and characterization of GRK5,a member of the family of G protein-coupled receptor kinases.Biol Chem,1994,269:6832-6841.
53.Kunapuli P,Gurevieh VV,Benovic JL.Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRKS.J Biol Chem,1994,269:10209-10212.
54.Chuang DM,Costa E.Evidence for internalization of the recognition site of β-adrenergie receptors during receptor subsensitivity induced by isoproterenol.Proc Natl Acad Sci USA,1979,76:3024-3028.
55.Staehelin M,Simons P.Rapid and reversible disappearance of β-adrenergic cell surface receptors.EMBO J,1982,1:187-190.
56.Barak LS,Ferguson SSG,Zhang J,et al.Internal trafficking and surface mobility of a functionally intact 2-adrenergie receptor-green fluorescent protein conjugate.Mol Pharmacol,1997a,51:177-184.
57.Ferguson G,Watterson KR,Palmer TM.Subtype-specific kinetics of inhibitory adenosine receptor intemalization are determined by sensitivity to phosphorylation by G protein-coupled receptor kinases.Mol Pharmacol,2000,57:546-552.
58.Hausd(?)ff WP Bouvier M,O'Dowd RF,et al.(?)phorylation sites(?)two domains of the 2-adrenergic receptor are involved in distinct pathways of receptor desensitization.J Biol Chem,1989,264:12657-1266.
59.Moro O,Lameh J,Sadee W.Serine-and threonine-rich domain regulates internalization of muscarinic cholinergic receptors.J Biol Chem,1993,268:6862-6865
60.Tsuga(?),Kameyama K,Haga T,et al.Sequesuation of muscarinic acet(?)choline receptor m2 subtypes:Facilitation by G protein-coupled receptor kinase(GRK2)and attenuation by a dominant-negative mutant of GRK2.J Biol Chem,1994,269:32522-32527.
61.Barlic J,Khandaker LS,Mahon MH,et al.β-Arresfins regulate interleukin-8(IL-8)-induced CXCR1 internalization.J Biol Chem,1999,274:16287-16294.