尾加压素Ⅱ对心血管反射及中枢神经元的调控作用
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摘要
尾加压素Ⅱ(urotensin II, UII)是20世纪80年代从鱼的脊髓尾部下垂体中分离出来的一种“生长抑素”样环肽。研究发现人体内存在一种孤立的G蛋白偶联受体(G-protein coupled receptor)GPR14,是UⅡ的特异性受体,主要分布于心血管系统和神经系统。UII与心肌细胞上此受体结合后使细胞内的Ca2+浓度增加,引起一系列的心血管效应。UII是迄今所知最强的缩血管物质,在两栖类动物,引起动脉条浓度依赖性收缩反应;在哺乳类动物,低浓度时可使动脉条产生内皮依赖性的松弛反应,而高浓度时则引起动脉条非内皮依赖性收缩反应。大剂量UII除引起心动过缓外,还引起持续的心输出量减少。UⅡ除作用于心血管系统外,还具有调节内分泌和渗透压的作用,并有促细胞增殖效应。血浆中UII的水平在高血压、心衰、糖尿病、肾病等多种疾病状态下有所升高。然而,有关UII如何参与调节血压的心血管反射,特别是对中枢神经元的作用如何,目前仍不十分明确,本文主要通过在体和离体的动物实验,利用循环生理学、电生理学、激光共聚焦显微镜、免疫组化等方法,从以下几个方面进行了研究:(1)采用隔离灌流颈动脉窦区,记录动脉血压变化的方法,观察UII对参与调节血压的重要的心血管反射——动脉压力感受器反射的影响。(2)采用玻璃微电极细胞外记录神经元单位放电技术,观察UII对大鼠海马脑片神经元自发放电的影响,并探讨其可能的作用机制。(3)采用玻璃微电极细胞外记录神经元单位放电技术,观察UII对大鼠下丘脑脑片室旁核神经元自发放电的影响,并探讨其可能的作用机制。(4)采用Fluo3-AM负载培养的海马神经元,用激光共聚焦法测定单个神经元细胞内[Ca2+]i的荧光强度,观察UII对海马神经元细胞内游离的钙离子浓度([Ca2+]i)的影响。(5)利用Fos蛋白免疫组化方法,研究侧脑室注射UII对大鼠心血管相关核团中c-fos的表达的影响。
1尾加压素II对大鼠颈动脉压力感受器反射的影响及其机制
采用隔离灌流麻醉大鼠颈动脉窦技术,观察了尾加压素II对颈动脉窦压力感受器反射的影响。其结果如下:(1)UII (30.0, 300.0, 3000.0nmol/L)
Urotensin II (UII) is a vasoactive‘somatostatin-like’cyclic peptide which was originally isolated from fish spinal cords, and has recently been cloned from man. The orphan receptor GPR14, a G-protein-coupled receptor first cloned from rat, has been defined as the specific receptor for UII. Positive immunoreactive staining for human UII and GPR14 mRNA was detected in both atrial and ventricular tissues. These studies indicate that UII might act as one of endogenous modulators of cardiac function. The cardiovascular action of UII has been examined in a number of in vitro and in vivo systems, sometimes with contrasting responses dependenting on the species and vessel studied. In mammals, UII was first reported to have a vasoconstrictor action in isolated rat thoracic aorta denuded of endothelium, an action that was later shown to be more potent than that of endothelin. UII was also shown to cause vasoconstriction in endothelium-denuded vessels from various species. In contrast, UII caused vasodilation in human small pulmonary arteries and abdominal adipose tissue arteries. In addition, the cardiovascular responses to UII in vivo are equally variable. Systemic administration of human UII to monkeys elicited a fall in cardiac output, severe myocardial contractility depression, and fatal circulatory failure. In anesthetized rats UII administered IV decreased arterial pressure. While in conscious rat IV UII reduced arterial pressure, the hypotension was associated with mesenteric and hindquarter vasodilatation. Although UII acts as a strong vasoactive peptide, it has been recently reported that central UII may play cardiovascular roles in the CNS, such as paraventricular nucleus of hypothamus (PVN), arcuate nucleus, A1 and A2 area. Intracerebroventricular (ICV) administration of UII significantly increased mean arterial pressure (MAP) and heart rate (HR) both in conscious rats and in anesthetized rats. Similarly, MAP and HR were increased after
1尾加压素II对大鼠颈动脉压力感受器反射的影响及其机制
采用隔离灌流麻醉大鼠颈动脉窦技术,观察了尾加压素II对颈动脉窦压力感受器反射的影响。其结果如下:(1)UII (30.0, 300.0, 3000.0nmol/L)
Urotensin II (UII) is a vasoactive‘somatostatin-like’cyclic peptide which was originally isolated from fish spinal cords, and has recently been cloned from man. The orphan receptor GPR14, a G-protein-coupled receptor first cloned from rat, has been defined as the specific receptor for UII. Positive immunoreactive staining for human UII and GPR14 mRNA was detected in both atrial and ventricular tissues. These studies indicate that UII might act as one of endogenous modulators of cardiac function. The cardiovascular action of UII has been examined in a number of in vitro and in vivo systems, sometimes with contrasting responses dependenting on the species and vessel studied. In mammals, UII was first reported to have a vasoconstrictor action in isolated rat thoracic aorta denuded of endothelium, an action that was later shown to be more potent than that of endothelin. UII was also shown to cause vasoconstriction in endothelium-denuded vessels from various species. In contrast, UII caused vasodilation in human small pulmonary arteries and abdominal adipose tissue arteries. In addition, the cardiovascular responses to UII in vivo are equally variable. Systemic administration of human UII to monkeys elicited a fall in cardiac output, severe myocardial contractility depression, and fatal circulatory failure. In anesthetized rats UII administered IV decreased arterial pressure. While in conscious rat IV UII reduced arterial pressure, the hypotension was associated with mesenteric and hindquarter vasodilatation. Although UII acts as a strong vasoactive peptide, it has been recently reported that central UII may play cardiovascular roles in the CNS, such as paraventricular nucleus of hypothamus (PVN), arcuate nucleus, A1 and A2 area. Intracerebroventricular (ICV) administration of UII significantly increased mean arterial pressure (MAP) and heart rate (HR) both in conscious rats and in anesthetized rats. Similarly, MAP and HR were increased after
引文
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2 Conlon JM,Yano K,Waugh D,et al. Distribution and molecular forms of urotensinⅡ and its role in cardiovascular regulation in vertebrates. J Exp Zool, 1996, 275: 226-238.
3 Coulouarn Y, Lihrmann I, Jegou S, et al. Cloning of cDNA encoding the urotensinⅡprecursor in frog and human reveals intense expression of the urotensinⅡgene in motoneurons of the spinal cord. Proc Natl Acad Sci USA, 1998, 95: 15803-15808.
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5 Liu QY, Pong SS, Zeng ZZ, et al. Identification of urotensinⅡ as the endogenous ligand for the orphan G-protein coupled receptor GPR14. Biochem Biophys Res Co, 1999, 266: 174-178.
6 Mori M, Sugo T, Abe M, et al. Human urotensinⅡ is the endogenous ligand of a G-protein coupled receptor, SENR (GPR14). Biochem Biophys Res Co, 1999, 265: 123-129.
7 Nothacker HP, Wang Z, McNeill, et al. Identification of the natural ligand of an orphan G-protein coupled receptor involved in the regulation of vasoconstriction. Nat Cell Biol, 1999, 1: 383-385.
8 Anna MD, Watson, Clive N, et al. UrotensinⅡ, a novel peptide in central and peripheral cardiovascular control. Peptide, 2004, 25: 1759-1766.
9 Lin Y, Tsuchihashi T, Matsumura K, et al. Central cardiovascular action of urotensinⅡin conscious rats. J Hypertens, 2003, 21: 159-165.
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11 Lu Y, Zou C, Huang D, et al. Cardiovascular effects of urotensinⅡin different brain areas. Peptides, 2003, 23: 1631-1635.
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1 Chartel N, Conlon JM, Collin F, Braun B, Waugh D, Vallarino M. Urotensin II in the central nervous system of the frog Rana ridibunda. Biochemical characterization and Immunohistochemical localization. Ann N Y Acad Sci 1998; 839:506-507.
2 Conlon J M,Yano K,Waugh D,Hazon N. Distribution and molecular forms of urotensin II and its role in cardiovascular regulation in vertebrates. J Exp Zool 1996; 275: 226-238.
3 Ames RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, Louden CS, Foley JJ, Sauermelch CF, Coatney RW, Ao ZH, Disa J, Holmes SD, Stadel JM, Martin JD, Liu WS, Glover GI, Wilson S, McNulty DE, Ellis CE, Elshourbagy NA, Shabon U, Trill JJ, Hay DWP, Ohlstein EH, Bergsma DJ, Douglas SA. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 1999; 401: 282-286.
4 Liu QY, Pong SS, Zeng ZZ, Zhang Q, Howard AD, Williams DL, Davidoff M, Wang RP, Austin CP, McDonald TP, Bai C, George SR, Evans JF, Caskey CT. Identification of urotensin II as the endogenous ligand for the orphan G-protein coupled receptor GPR14. Biochem Biophys Res Commun 1999; 266: 174-178.
5 Mori M, Sugo T, Abe M, Shimomura Y, Kurihara M, Kitada C, Kikuchi K, Shintani Y, Kurokawa T, Onda H, Nishimura O, Fujino M. Human urotensin II is the endogenous ligand of a G-protein coupled receptor, SENR (GPR14). Biochem Biophys Res Commun 1999; 265: 123-129.
6 Anna M.D, Watson, Clive N. May. Urotensin II, a novel peptide in central and peripheral cardiovascular control. Peptide 2004; 25: 1759-1766.
7 Lin Y, Tsuchihashi T, Matsumura K, Abe I, Iida M. Central cardiovascular action of urotensin II in conscious rats. J Hypert 2003; 21: 159-165.
8 Lin Y, Tsuchihashi T, Matsumura K, Fukuhara M, Ohya Y, Fujii K. Central cardiovascular action of urotensin II in spontaneously hypertensive rats. Hypertens Res 2003; 26: 839-845.
9 Gartlon J, Parker F, Harrison DC, Douglas SA, Ashmeade TE, Riley GJ, Hughes ZA, Taylor SG, Munton RP, Hagan JJ, Hunter JA, Jones DN. Central effects of urotensin II following ICV administration in rats. Psychopharmacology 2001; 155: 426-433.
10 Lu Y, Zou C, Huang D, Tang C. Cardiovascular effects of urotensin II in different brain areas. Peptides 2003; 23: 1631-1635.
11 Gibson A, Wallace P, Bern HA. Cardiovascular effects of urotensin II in anesthetized and pitched rats. Gen Comp Endocrinol, 1986; 64:435-439.
12 Waston AM, Lambert GM, Smith KJ, May CN. Urotensin II acts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actions. Hypertension 2003; 42: 373-379.
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2 Chartel N, Conlon JM, Collin F, Braun B, Waugh D, Vallarino M. UrotensinⅡin the central nervous system of the frog Rana ridibunda. Biochemical characterization and Immunohistochemical localization. Ann N Y Acad Sci 1998; 839:506-507.
3 Conlon J M,Yano K,Waugh D,Hazon N. Distribution and molecular forms of urotensin Ⅱ and its role in cardiovascular regulation in vertebrates. J Exp Zool 1996; 275: 226-238.
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5 Ames RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, Louden CS, Foley JJ, Sauermelch CF, Coatney RW, Ao ZH, Disa J, Holmes SD, Stadel JM, Martin JD, Liu WS, Glover GI, Wilson S, McNulty DE, Ellis CE, Elshourbagy NA, Shabon U, Trill JJ, Hay DWP, Ohlstein EH, Bergsma DJ, Douglas SA. Human urotensinⅡ is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 1999; 401: 282-286.
6 Liu QY, Pong SS, Zeng ZZ, Zhang Q, Howard AD, Williams DL, Davidoff M, Wang RP, Austin CP, McDonald TP, Bai C, George SR, Evans JF, Caskey CT. Identification of urotensinⅡ as the endogenous ligand for the orphan G-protein coupled receptor GPR14. Biochem Biophys Res Commun 1999; 266: 174-178.
7 Mori M, Sugo T, Abe M, Shimomura Y, Kurihara M, Kitada C, Kikuchi K, Shintani Y, Kurokawa T, Onda H, Nishimura O, Fujino M. Human urotensinⅡ is the endogenous ligand of a G-protein coupled receptor, SENR (GPR14). Biochem Biophys Res Commun 1999; 265: 123-129.
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9 Gibson A, Wallace P, Bern HA. Cardiovascular effects of urotensin II in anesthetized and pitched rats. Gen Comp Endocrinol 1986; 64:435-439.
10 Lin Y, Tsuchihashi T, Matsumura K, Abe I, Iida M. Central cardiovascular action of urotensinⅡin conscious rats. J Hypertens 2003; 21: 159-165.
11 Lin Y, Tsuchihashi T, Matsumura K, Fukuhara M, Ohya Y, Fujii K. Central cardiovascular action of urotensin II in spontaneously hypertensive rats. Hypertens Res 2003; 26: 839-845.
12 Wu YM, Wang R, He RR. UrotensinⅡinhibits electrical activity of hippocampal CA1 neurons by potentiating the GABAA receptor-mediated Cl- current. Neurosci Bull, 2006,22(2):110-114.
13 Waston AM, Lambert GM, Smith KJ, May CN. UrotensinⅡacts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actions. Hypertension 2003; 42: 373-379.
14 Gartlon J, Parker F, Harrison DC, Douglas SA, Ashmeade TE, Riley GJ, Hughes ZA, Taylor SG, Munton RP, Hagan JJ, Hunter JA, Jones DN. Central effects of urotensin Ⅱ following ICV administration in rats. Psychopharmacology 2001; 155: 426-433.
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5 Mori M, Sugo T, Abe M, et al. Human urotensinⅡ is the endogenous ligand of a G-protein coupled receptor SENR (GPR14). Biochem Biophys Res Commun, 1999, 265(1): 123-129.
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9 Conlon J M,Yano K,Waugh D,et al. Distribution and molecular forms of urotensinⅡ and its role in cardiovascular regulation in vertebrates. J Exp Zool, 1996, 275: 226-238.
10 Gibson A, Wallace P, Bern HA. Cardiovascular effects of urotensin II in anesthetized and pitched rats. Gen Comp Endocrinol, 1986, 64:435-439.
11 Lin Y, Tsuchihashi T, Matsumura K, et al. Central cardiovascular action ofurotensinⅡin conscious rats. J Hypertens, 2003, 21: 159-165.
12 Lin Y, Tsuchihashi T, Matsumura K, et al. Central cardiovascular action of urotensin II in spontaneously hypertensive rats. Hypertens Res, 2003, 26: 839-845.
13 Filipeanu CM, Brailoiu E, Le Dun S, et al. Urotensin-II regulates intracellular calcium in dissociated rat spinal cord neurons. J Nurochem, 2002, 83: 879-884.
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22 Waston AM, Lambert GM, Smith KJ, May CN. Urotensin II acts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actions. Hypertension 2003, 42: 373-379.
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2 Ames RS, Sarau HM, Chambers JK, et al. Human urotensinⅡ is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature, 1999, 401(6750): 282-286.
3 Gibon A. Complex effects of Gillichthys urotensin II on rat aortic strips. Br J Pharmacol, 1987, 91: 205-212.
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8 Mori M, Sugo T, Abe M, et al. Human urotensinⅡ is the endogenous ligand of a G-protein coupled receptor SENR (GPR14). Biochem Biophys Res Commun, 1999, 265(1): 123-129.
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1 Chartel N, Conlon JM, Collin F, et al. UrotensinⅡin the central nervous system of the frog Rana ridibunda. Biochemical characterization and Immunohistochemical localization. Ann NY Acad Sci, 1998, 839:506-507.
2 Conlon JM,Yano K,Waugh D,et al. Distribution and molecular forms of urotensinⅡ and its role in cardiovascular regulation in vertebrates. J Exp Zool, 1996, 275: 226-238.
3 Coulouarn Y, Lihrmann I, Jegou S, et al. Cloning of cDNA encoding the urotensinⅡprecursor in frog and human reveals intense expression of the urotensinⅡgene in motoneurons of the spinal cord. Proc Natl Acad Sci USA, 1998, 95: 15803-15808.
4 Ames RS, Sarau HM, Chambers JK, et al. Human urotensinⅡ is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature, 1999, 401: 282-286.
5 Liu QY, Pong SS, Zeng ZZ, et al. Identification of urotensinⅡ as the endogenous ligand for the orphan G-protein coupled receptor GPR14. Biochem Biophys Res Co, 1999, 266: 174-178.
6 Mori M, Sugo T, Abe M, et al. Human urotensinⅡ is the endogenous ligand of a G-protein coupled receptor, SENR (GPR14). Biochem Biophys Res Co, 1999, 265: 123-129.
7 Nothacker HP, Wang Z, McNeill, et al. Identification of the natural ligand of an orphan G-protein coupled receptor involved in the regulation of vasoconstriction. Nat Cell Biol, 1999, 1: 383-385.
8 Anna MD, Watson, Clive N, et al. UrotensinⅡ, a novel peptide in central and peripheral cardiovascular control. Peptide, 2004, 25: 1759-1766.
9 Lin Y, Tsuchihashi T, Matsumura K, et al. Central cardiovascular action of urotensinⅡin conscious rats. J Hypertens, 2003, 21: 159-165.
10 Lin Y, Tsuchihashi T, Matsumura K, et al. Central cardiovascular action of urotensinⅡin spontaneously hypertensive rats. Hypertens Res, 2003,26: 839-845.
11 Lu Y, Zou C, Huang D, et al. Cardiovascular effects of urotensinⅡin different brain areas. Peptides, 2003, 23: 1631-1635.
12 Waston AM, Lambert GM, Smith KJ, et al. UrotensinⅡacts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actions. Hypertension, 2003, 42: 373-379.
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15 Sawada M, Ichinose M. Potentiation of GABAA receptor-mediated Cl- current by urotensin peptide in identified Aplysia neurons. J Neurosci Res, 1999, 56: 547-552.
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18 Hasegawa K, Kobayashi Y, Kogayashi H. Vasodepressor effects of urotensin II in rats. Neurosci Lett, 1992, 14:357-363.
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1 Chartel N, Conlon JM, Collin F, Braun B, Waugh D, Vallarino M. Urotensin II in the central nervous system of the frog Rana ridibunda. Biochemical characterization and Immunohistochemical localization. Ann N Y Acad Sci 1998; 839:506-507.
2 Conlon J M,Yano K,Waugh D,Hazon N. Distribution and molecular forms of urotensin II and its role in cardiovascular regulation in vertebrates. J Exp Zool 1996; 275: 226-238.
3 Ames RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, Louden CS, Foley JJ, Sauermelch CF, Coatney RW, Ao ZH, Disa J, Holmes SD, Stadel JM, Martin JD, Liu WS, Glover GI, Wilson S, McNulty DE, Ellis CE, Elshourbagy NA, Shabon U, Trill JJ, Hay DWP, Ohlstein EH, Bergsma DJ, Douglas SA. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 1999; 401: 282-286.
4 Liu QY, Pong SS, Zeng ZZ, Zhang Q, Howard AD, Williams DL, Davidoff M, Wang RP, Austin CP, McDonald TP, Bai C, George SR, Evans JF, Caskey CT. Identification of urotensin II as the endogenous ligand for the orphan G-protein coupled receptor GPR14. Biochem Biophys Res Commun 1999; 266: 174-178.
5 Mori M, Sugo T, Abe M, Shimomura Y, Kurihara M, Kitada C, Kikuchi K, Shintani Y, Kurokawa T, Onda H, Nishimura O, Fujino M. Human urotensin II is the endogenous ligand of a G-protein coupled receptor, SENR (GPR14). Biochem Biophys Res Commun 1999; 265: 123-129.
6 Anna M.D, Watson, Clive N. May. Urotensin II, a novel peptide in central and peripheral cardiovascular control. Peptide 2004; 25: 1759-1766.
7 Lin Y, Tsuchihashi T, Matsumura K, Abe I, Iida M. Central cardiovascular action of urotensin II in conscious rats. J Hypert 2003; 21: 159-165.
8 Lin Y, Tsuchihashi T, Matsumura K, Fukuhara M, Ohya Y, Fujii K. Central cardiovascular action of urotensin II in spontaneously hypertensive rats. Hypertens Res 2003; 26: 839-845.
9 Gartlon J, Parker F, Harrison DC, Douglas SA, Ashmeade TE, Riley GJ, Hughes ZA, Taylor SG, Munton RP, Hagan JJ, Hunter JA, Jones DN. Central effects of urotensin II following ICV administration in rats. Psychopharmacology 2001; 155: 426-433.
10 Lu Y, Zou C, Huang D, Tang C. Cardiovascular effects of urotensin II in different brain areas. Peptides 2003; 23: 1631-1635.
11 Gibson A, Wallace P, Bern HA. Cardiovascular effects of urotensin II in anesthetized and pitched rats. Gen Comp Endocrinol, 1986; 64:435-439.
12 Waston AM, Lambert GM, Smith KJ, May CN. Urotensin II acts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actions. Hypertension 2003; 42: 373-379.
13 de Wardener HE. The hypothalamus and hypertension. Physiol Rev, 2001, 81:1599-1658.
14 Allen AM. Inhibition of the hypothalamic paraventricular nucleus in spontaneously hypertensive rats dramatically reduces sympathetic vasomotor tone. Hypertension, 2002, 39:275-280.
15 Riboni L, Luna F and Nunez-Duran H. A fast staining method for CNS slices. J Neurosci Methods, 1991,38:239-241.
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17 Sawada M, Ichinose M. Potentiation of GABAA receptor-mediated Cl- current by urotensin peptide in identified Aplysia neurons. J Neurosci Res 1999; 56: 547-552.
18 Clark SD, Nothacker HP, Blaha CD, Tyler CJ, Duangdao DM, Grupke SL, Helton DR, Leonard CS, Civelli O. Urotensin II acts as a modulator of mesopontine cholinergic neurons. Brain Res 2005; 1059: 139-148.
19 Huitron-Resendiz S, Kristensen MP, Sanchez-Alavez M, Clark SD, Grupke SL, Tyler C, Suzuki C, Nothacker HP, Civelli O, Criado JR, Henriksen SJ, Leonard CS, de Lecea L. Urotensin II modulates rapid eyemovement sleep through activation of brainstem cholinergic neurons. J Neurosci 2005; 25: 5465-5474.
20 Li DP, Chen SR, Pan HL. Nitric oxide inhibits spinally projecting paraventricular neurons through potentiation of presynaptic GABA release. J Neurophysiol 2002; 88:2664-2674.
21 Xue BJ, Wang ZA, He RR. Effects of NO precursor and donor on neuronal activity of rat hippocampal slices. Acta Physiol Sin 1997; 49: 375 - 381 (Chinese, English abstract).
22 Hasegawa K, Kobayashi Y, Kogayashi H. Vasodepressor effects of urotensin II in rats. Neurosci Lett 1992, 14:357-363.
1 Pearson D, Shiverly JE, Clark BR, et al. Urotensin II: a somatostation like peptide in the caudal neurosecretory system of fishes. Proc Natl Acad Sci USA, 1980, 77:5021-5024.
2 Chartel N, Conlon JM, Collin F, Braun B, Waugh D, Vallarino M. UrotensinⅡin the central nervous system of the frog Rana ridibunda. Biochemical characterization and Immunohistochemical localization. Ann N Y Acad Sci 1998; 839:506-507.
3 Conlon J M,Yano K,Waugh D,Hazon N. Distribution and molecular forms of urotensin Ⅱ and its role in cardiovascular regulation in vertebrates. J Exp Zool 1996; 275: 226-238.
4 Coulouarn Y, Lihrmann I, Jegou s, Jegou S, Anouar Y, Tostivint H, Beauvillain JC, Conlon JM, Bern HA, Vaudry H. Cloning of cDNA encoding the urotensinⅡprecursor in frog and human reveals intense expression of the urotensinⅡgene in motoneurons of the spinal cord. Proc Natl Acad Sci. USA 1998; 95: 15803-15808.
5 Ames RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, Louden CS, Foley JJ, Sauermelch CF, Coatney RW, Ao ZH, Disa J, Holmes SD, Stadel JM, Martin JD, Liu WS, Glover GI, Wilson S, McNulty DE, Ellis CE, Elshourbagy NA, Shabon U, Trill JJ, Hay DWP, Ohlstein EH, Bergsma DJ, Douglas SA. Human urotensinⅡ is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 1999; 401: 282-286.
6 Liu QY, Pong SS, Zeng ZZ, Zhang Q, Howard AD, Williams DL, Davidoff M, Wang RP, Austin CP, McDonald TP, Bai C, George SR, Evans JF, Caskey CT. Identification of urotensinⅡ as the endogenous ligand for the orphan G-protein coupled receptor GPR14. Biochem Biophys Res Commun 1999; 266: 174-178.
7 Mori M, Sugo T, Abe M, Shimomura Y, Kurihara M, Kitada C, Kikuchi K, Shintani Y, Kurokawa T, Onda H, Nishimura O, Fujino M. Human urotensinⅡ is the endogenous ligand of a G-protein coupled receptor, SENR (GPR14). Biochem Biophys Res Commun 1999; 265: 123-129.
8 Nothacker HP, Wang Z, McNeill AM,Saito Y, Mrten S, O’Dowd B, Duckles SP, Civelli O. Identification of the natural ligand of an orphan G-protein coupled receptor involved in the regulation of vasoconstriction. Nat Cell Biol 1999; 1: 383-385.
9 Gibson A, Wallace P, Bern HA. Cardiovascular effects of urotensin II in anesthetized and pitched rats. Gen Comp Endocrinol 1986; 64:435-439.
10 Lin Y, Tsuchihashi T, Matsumura K, Abe I, Iida M. Central cardiovascular action of urotensinⅡin conscious rats. J Hypertens 2003; 21: 159-165.
11 Lin Y, Tsuchihashi T, Matsumura K, Fukuhara M, Ohya Y, Fujii K. Central cardiovascular action of urotensin II in spontaneously hypertensive rats. Hypertens Res 2003; 26: 839-845.
12 Wu YM, Wang R, He RR. UrotensinⅡinhibits electrical activity of hippocampal CA1 neurons by potentiating the GABAA receptor-mediated Cl- current. Neurosci Bull, 2006,22(2):110-114.
13 Waston AM, Lambert GM, Smith KJ, May CN. UrotensinⅡacts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actions. Hypertension 2003; 42: 373-379.
14 Gartlon J, Parker F, Harrison DC, Douglas SA, Ashmeade TE, Riley GJ, Hughes ZA, Taylor SG, Munton RP, Hagan JJ, Hunter JA, Jones DN. Central effects of urotensin Ⅱ following ICV administration in rats. Psychopharmacology 2001; 155: 426-433.
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1 Pearson D, Shively DE, Clark BR. Urotensin II: a somatostatin-like peptide in the caudal neurosecretory system of fishes. Proc Natl Acad Sci USA, 1980, 77: 5021-5024.
2 Bern HA, Pearson D, Larson BA, et al. Neurohormones from fish tail: the caudal neurosecretory system. I:’urophysiology’ and the caudal neruosecretory system of fishes. Recent Prog Horm Res, 1985, 41:533-552.
3 Ames RS, Sarau HM, Chambers JK, et al. Human urotensinⅡ is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature, 1999, 401: 282-286.
4 Liu Q, Pong SS, Zeng Z, et al. Identification of urotensinⅡ as the endogenous ligand for the orphan G-protein coupled receptor GPR14. Biochem Biophys Res Commun, 1999, 266(1): 174-178.
5 Mori M, Sugo T, Abe M, et al. Human urotensinⅡ is the endogenous ligand of a G-protein coupled receptor SENR (GPR14). Biochem Biophys Res Commun, 1999, 265(1): 123-129.
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