The role of urocortins in the cardiovascular system

Journal of Physiology and Pharmacology

Volumn 65, Issue 6, 2014, Pages 753-766

  Walczewska, Jolanta ^a   Dzieza Grudnik, A ^a   Siga, O ^a   Grodzicki, T ^a  

^a JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE   (Poland)

Author keywords

Cardioprotection; Cardiovascular diseases; Corticotropin releasing hormone receptor 1; Corticotropin releasing hormone receptor 2; Urocortin 1; Urocortin 2; Urocortin 3; Vasodilation

Indexed keywords

CORTICOTROPIN; CORTICOTROPIN RELEASING FACTOR; ESMOLOL; FUROSEMIDE; G PROTEIN COUPLED RECEPTOR; UROCORTIN; UROCORTIN I; UROCORTIN II; UROCORTIN III; CORTICOTROPIN RELEASING FACTOR RECEPTOR;

ADRENERGIC SYSTEM; ANTIHYPERTENSIVE ACTIVITY; AORTA ANEURYSM; BINDING AFFINITY; BLOOD VESSEL INJURY; CARDIOVASCULAR SYSTEM; CONGESTIVE HEART FAILURE; HEART PROTECTION; HEMODYNAMICS; HUMAN; HYPERTENSION; INOTROPISM; ISCHEMIC HEART DISEASE; NONHUMAN; PROTEIN METABOLISM; PROTEIN STRUCTURE; REGULATORY MECHANISM; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REPERFUSION INJURY; REVIEW; SEQUENCE ALIGNMENT; STRESS; VASODILATATION; ANIMAL; CARDIOVASCULAR DISEASE; METABOLISM;

ANIMALS; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; CORTICOTROPIN-RELEASING HORMONE; HEMODYNAMICS; HUMANS; RECEPTORS, CORTICOTROPIN-RELEASING HORMONE; UROCORTINS;

EID: 84919958706     PISSN: 08675910     EISSN: 18991505     Source Type: Journal    
DOI: None     Document Type: Review

References (151)

1. Heinrichs SC, Koob GF. Corticotropin-releasing factor in brain: a role in activation, arousal, and affect regulation. J Pharmacol Exp Ther 2004; 311: 427-440.
2. Neufeld-Cohen A, Tsoory MM, Evans AK, et al. A triple urocortin knockout mouse model reveals an essential role for urocortins in stress recovery. Proc Natl Acad Sci USA 2010; 107: 19020-19025.
3. Zorrilla EP, Tache Y, Koob GF. Nibbling at CRF receptor control of feeding and gastrocolonic motility. Trends Pharmacol Sci 2003; 24: 421-427.
4. Stengel A, Tache Y. Corticotropin-releasing factor signaling and visceral response to stress. Exp Biol Med (Maywood) 2010; 235: 1168-1178.
5. Larauche M, Kiank C, Tache Y. Corticotropin releasing factor signaling in colon and ileum: regulation by stress and pathophysiological implications. J Physiol Pharmacol 2009; 60 (Suppl 7): 33-46.
6. Fekete EM, Zorrilla EP. Physiology, pharmacology, and therapeutic relevance of urocortins in mammals: ancient CRF paralogs. Front Neuroendocrinol 2007; 28: 1-27.
7. Kageyama K. Regulation of gonadotropins by corticotropinreleasing factor and urocortin. Front Endocrinol (Lausanne) 2013; 4: 12.
8. De Bonis M, Torricelli M, Severi FM, Luisi S, De Leo V, Petraglia F. Neuroendocrine aspects of placenta and pregnancy. Gynecol Endocrinol 2012; 28 (Suppl 1): 22-26.
9. Vale W, Spiess J, Rivier C, Rivier J. Characterization of a 41- residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 1981; 213: 1394-1397.
10. Takahashi K. Distribution of urocortins and corticotropinreleasing factor receptors in the cardiovascular system. Int J Endocrinol 2012; 2012: 395284.
11. Onorati F, Chen-Scarabelli C, Knight R, et al. Targeting urocortin signaling pathways to enhance cardioprotection: is it time to move from bench to bedside? Cardiovasc Drugs Ther 2013; 27: 451-463.
12. Vaughan J, Donaldson C, Bittencourt J, et al. Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 1995; 378: 287-292.
13. Donaldson CJ, Sutton SW, Perrin MH, et al. Cloning and characterization of human urocortin. Endocrinology 1996; 137: 3896.
14. Hsu SY, Hsueh AJ. Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropinreleasing hormone receptor. Nat Med 2001; 7: 605-611.
15. Reyes TM, Lewis K, Perrin MH, et al. Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc Natl Acad Sci USA 2001; 98: 2843-2848.
16. Lewis K, Li C, Perrin MH, et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc Natl Acad Sci USA 2001; 98: 7570-7575.
17. Chen A, Vaughan J, Vale WW. Glucocorticoids regulate the expression of the mouse urocortin II gene: a putative connection between the corticotropin-releasing factor receptor pathways. Mol Endocrinol 2003; 17: 1622-1639.
18. Grace CR, Perrin MH, Cantle JP, Vale WW, Rivier JE, Riek R. Common and divergent structural features of a series of corticotropin releasing factor-related peptides. J Am Chem Soc 2007; 129: 16102-16114.
19. Grammatopoulos DK. Insights into mechanisms of corticotropin-releasing hormone receptor signal transduction. Br J Pharmacol 2012; 166: 85-97.
20. Potter E, Behan DP, Fischer WH, Linton EA, Lowry PJ, Vale WW. Cloning and characterization of the cDNAs for human and rat corticotropin releasing factor-binding proteins. Nature 1991; 349: 423-426.
21. Iino K, Sasano H, Oki Y, et al. Urocortin expression in the human central nervous system. Clin Endocrinol (Oxf) 1999; 50: 107-114.
22. Iino K, Sasano H, Oki Y, et al. Urocortin expression in human pituitary gland and pituitary adenoma. J Clin Endocrinol Metab 1997; 82: 3842-3850.
23. Weitemier AZ, Ryabinin AE. Lesions of the Edinger- Westphal nucleus alter food and water consumption. Behav Neurosci 2005; 119: 1235-1243.
24. Weninger SC, Peters LL, Majzoub JA. Urocortin expression in the Edinger-Westphal nucleus is up-regulated by stress and corticotropin-releasing hormone deficiency. Endocrinology 2000; 141: 256-263.
25. Bachtell RK, Tsivkovskaia NO, Ryabinin AE. Identification of temperature-sensitive neural circuits in mice using c-Fos expression mapping. Brain Res 2003; 960: 157-164.
26. Innis RB, Aghajanian GK. Cholecystokinin-containing and nociceptive neurons in rat Edinger-Westphal nucleus. Brain Res 1986; 363: 230-238.
27. Roste GK, Dietrichs E. Cerebellar cortical and nuclear afferents from the Edinger-Westphal nucleus in the cat. Anat Embryol (Berl) 1988; 178: 59-65.
28. Bachtell RK, Weitemier AZ, Galvan-Rosas A, et al. The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption. J Neurosci 2003; 23: 2477-2487.
29. Gaszner B, Csernus V, Kozicz T. Urocortinergic neurons respond in a differentiated manner to various acute stressors in the Edinger-Westphal nucleus in the rat. J Comp Neurol 2004; 480: 170-179.
30. Kozicz T, Korosi A, Korsman C, et al. Urocortin expression in the Edinger-Westphal nucleus is down-regulated in transgenic mice over-expressing neuronal corticotropinreleasing factor. Neuroscience 2004; 123: 589-594.
31. Seres J, Bornstein SR, Seres P, et al. Corticotropin-releasing hormone system in human adipose tissue. J Clin Endocrinol Metab 2004; 89: 965-970.
32. Kimura Y, Takahashi K, Totsune K, et al. Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart. J Clin Endocrinol Metab 2002; 87: 340-346.
33. Fukuda T, Takahashi K, Suzuki T, et al. Urocortin 1, urocortin 3/stresscopin, and corticotropin-releasing factor receptors in human adrenal and its disorders. J Clin Endocrinol Metab 2005; 90: 4671-4678.
34. Bamberger CM, Minas V, Bamberger AM, et al. Expression of urocortin in the extravillous human trophoblast at the implantation site. Placenta 2007; 28: 127-132.
35. Petraglia F, Florio P, Gallo R, et al. Human placenta and fetal membranes express human urocortin mRNA and peptide. J Clin Endocrinol Metab 1996; 81: 3807-3810.
36. Bamberger CM, Wald M, Bamberger AM, Ergun S, Beil FU, Schulte HM. Human lymphocytes produce urocortin, but not corticotropin-releasing hormone. J Clin Endocrinol Metab 1998; 83: 708-711.
37. Uzuki M, Sasano H, Muramatsu Y, et al. Urocortin in the synovial tissue of patients with rheumatoid arthritis. Clin Sci (Lond) 2001; 100: 577-589.
38. Kempuraj D, Papadopoulou NG, Lytinas M, et al. Corticotropin-releasing hormone and its structurally related urocortin are synthesized and secreted by human mast cells. Endocrinology 2004; 145: 43-48.
39. Harada S, Imaki T, Naruse M, Chikada N, Nakajima K, Demura H. Urocortin mRNA is expressed in the enteric nervous system of the rat. Neurosci Lett 1999; 267: 125-128.
40. Kozicz T, Arimura A. Distribution of urocortin in the rat's gastrointestinal tract and its colocalization with tyrosine hydroxylase. Peptides 2002; 23: 515-521.
41. Kageyama K, Bradbury MJ, Zhao L, Blount AL, Vale WW. Urocortin messenger ribonucleic acid: tissue distribution in the rat and regulation in thymus by lipopolysaccharide and glucocorticoids. Endocrinology 1999; 140: 5651-5658.
42. Slominski A, Wortsman J, Pisarchik A, et al. Cutaneous expression of corticotropin-releasing hormone (CRH), urocortin, and CRH receptors. FASEB J 2001; 15: 1678-1693.
43. Imperatore A, Florio P, Torres PB, et al. Urocortin 2 and urocortin 3 are expressed by the human placenta, deciduas, and fetal membranes. Am J Obstet Gynecol 2006; 195: 288-295.
44. Yamauchi N, Otagiri A, Nemoto T, et al. Distribution of urocortin 2 in various tissues of the rat. J Neuroendocrinol 2005; 17: 656-663.
45. Takahashi K, Totsune K, Murakami O, Shibahara S. Urocortins as cardiovascular peptides. Peptides 2004; 25: 1723-1731.
46. Li C, Chen P, Vaughan J, et al. Urocortin III is expressed in pancreatic beta-cells and stimulates insulin and glucagon secretion. Endocrinology 2003; 144: 3216-3224.
47. Saruta M, Takahashi K, Suzuki T, Fukuda T, Torii A, Sasano H. Urocortin 3/stresscopin in human colon: possible modulators of gastrointestinal function during stressful conditions. Peptides 2005; 26: 1196-1206.
48. Patel K, Rademaker MT, Kirkpatrick CM, et al. Comparative pharmacokinetics and pharmacodynamics of urocortins 1, 2 and 3 in healthy sheep. Br J Pharmacol 2012; 166: 1916-1925.
49. Potter E, Sutton S, Donaldson C, et al. Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary. Proc Natl Acad Sci USA 1994; 91: 8777-8781.
50. Nishikimi T, Miyata A, Horio T, et al. Urocortin, a member of the corticotropin-releasing factor family, in normal and diseased heart. Am J Physiol Heart Circ Physiol 2000; 279: H3031-H3039.
51. Wiley KE, Davenport AP. CRF2 receptors are highly expressed in the human cardiovascular system and their cognate ligands urocortins 2 and 3 are potent vasodilators. Br J Pharmacol 2004; 143: 508-514.
52. Van Pett K, Viau V, Bittencourt JC, et al. Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse. J Comp Neurol 2000; 428: 191-212.
53. Lovenberg TW, Liaw CW, Grigoriadis DE, et al. Cloning and characterization of a functionally distinct corticotropinreleasing factor receptor subtype from rat brain. Proc Natl Acad Sci USA 1995; 92: 836-840.
54. Parkes DG, Vaughan J, Rivier J, Vale W, May CN. Cardiac inotropic actions of urocortin in conscious sheep. Am J Physiol 1997; 272: H2115-H2122.
55. Terui K, Higashiyama A, Horiba N, Furukawa KI, Motomura S, Suda T. Coronary vasodilation and positive inotropism by urocortin in the isolated rat heart. J Endocrinol 2001; 169: 177-183.
56. Kageyama K, Gaudriault GE, Bradbury MJ, Vale WW. Regulation of corticotropin-releasing factor receptor type 2 beta messenger ribonucleic acid in the rat cardiovascular system by urocortin, glucocorticoids, and cytokines. Endocrinology 2000; 141: 2285-2293.
57. Nazarloo HP, Nishiyama M, Tanaka Y, Asaba K, Hashimoto K. Down-regulation of corticotropin-releasing hormone receptor type 2beta mRNA expression in the rat cardiovascular system following food deprivation. Regul Pept 2002; 105: 121-129.
58. Pournajafi-Nazarloo H, Partoo L, Sanzenbacher L, Azizi F, Carter CS. Modulation of corticotropin-releasing hormone type 2 receptor and urocortin 1 and urocortin 2 mRNA expression in the cardiovascular system of prairie voles following acute or chronic stress. Neuroendocrinology 2007; 86: 17-25.
59. Kuizon E, Pearce EG, Bailey SG, et al.Mechanisms of action and clinical implications of cardiac urocortin: a journey from the heart to the systemic circulation, with a stopover in the mitochondria. Int J Cardiol 2009; 137: 189-194.
60. Davidson SM, Rybka AE, Townsend PA. The powerful cardioprotective effects of urocortin and the corticotropin releasing hormone (CRH) family. Biochem Pharmacol 2009; 77: 141-150.
61. Brar BK, Jonassen AK, Egorina EM, et al. Urocortin-II and urocortin-III are cardioprotective against ischemia reperfusion injury: an essential endogenous cardioprotective role for corticotropin releasing factor receptor type 2 in the murine heart. Endocrinology 2004; 145: 24-35.
62. Calderon-Sanchez E, Delgado C, Ruiz-Hurtado G, et al. Urocortin induces positive inotropic effect in rat heart. Cardiovasc Res 2009; 83: 717-725.
63. Yang LZ, Kockskamper J, Khan S, et al. cAMP- and Ca2+/calmodulin-dependent protein kinases mediate inotropic, lusitropic and arrhythmogenic effects of urocortin 2 in mouse ventricular myocytes. Br J Pharmacol 2011; 162: 544-556.
64. Yang LZ, Kockskamper J, Heinzel FR, et al. Urocortin II enhances contractility in rabbit ventricular myocytes via CRF(2) receptor-mediated stimulation of protein kinase A. Cardiovasc Res 2006; 69: 402-411.
65. Chanalaris A, Lawrence KM, Townsend PA, et al. Hypertrophic effects of urocortin homologous peptides are mediated via activation of the Akt pathway. Biochem Biophys Res Commun 2005; 328: 442-448.
66. Bale TL, Hoshijima M, Gu Y, et al. The cardiovascular physiologic actions of urocortin II: acute effects in murine heart failure. Proc Natl Acad Sci USA 2004; 101: 3697-3702.
67. Rademaker MT, Charles CJ, Espiner EA, et al. Beneficial hemodynamic, endocrine, and renal effects of urocortin in experimental heart failure: comparison with normal sheep. J Am Coll Cardiol 2002; 40: 1495-1505.
68. Weisinger RS, Blair-West JR, Burns P, et al. Cardiovascular effects of long-term central and peripheral administration of urocortin, corticotropin-releasing factor, and adrenocorticotropin in sheep. Endocrinology 2004; 145: 5598-5604.
69. Rademaker MT, Cameron VA, Charles CJ, Richards AM. Integrated hemodynamic, hormonal, and renal actions of urocortin 2 in normal and paced sheep: beneficial effects in heart failure. Circulation 2005; 112: 3624-3632.
70. Rademaker MT, Cameron VA, Charles CJ, Richards AM. Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure. Eur Heart J 2006; 27: 2088- 2098.
71. Rademaker MT, Charles CJ, Ellmers LJ, Lewis LK, Nicholls MG, Richards AM. Prolonged urocortin 2 administration in experimental heart failure: sustained hemodynamic, endocrine, and renal effects. Hypertension 2011; 57: 1136- 1144.
72. Rademaker MT, Charles CJ, Richards AM. Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure. Am J Physiol Heart Circ Physiol 2007; 293: H1536-H1544.
73. Davis ME, Pemberton CJ, Yandle TG, et al. Urocortin 2 infusion in human heart failure. Eur Heart J 2007; 28: 2589-2597.
74. Rademaker MT, Charles CJ, Nicholls MG, Richards AM. Urocortin 2 inhibits furosemide-induced activation of renin and enhances renal function and diuretic responsiveness in experimental heart failure. Circ Heart Fail 2009; 2: 532-540.
75. Rademaker MT, Charles CJ, Nicholls G, Richards M. Urocortin 2 sustains haemodynamic and renal function during introduction of beta-blockade in experimental heart failure. J Hypertens 2011; 29: 1787-1795.
76. Rademaker MT, Charles CJ, Nicholls MG, Richards AM. Interactions of enhanced urocortin 2 and mineralocorticoid receptor antagonism in experimental heart failure. Circ Heart Fail 2013; 6: 825-832.
77. Kageyama K, Teui K, Tamasawa N, Suda T. Regulation and roles of urocortins in the vascular system. Int J Endocrinol 2012; 2012: 873723.
78. Grossini E, Molinari C, Mary DA, et al. Urocortin II induces nitric oxide production through cAMP and Ca2+ related pathways in endothelial cells. Cell Physiol Biochem 2009; 23: 87-96.
79. Chen ZW, Huang Y, Yang Q, Li X, Wei W, He GW. Urocortin-induced relaxation in the human internal mammary artery. Cardiovasc Res 2005; 65: 913-920.
80. Huang Y, Chan FL, Lau CW, et al. Urocortin-induced endothelium-dependent relaxation of rat coronary artery: role of nitric oxide and K+ channels. Br J Pharmacol 2002; 135: 1467-1476.
81. Lau CW, Chan YC, Yao X, Chan FL, Chen ZY, Huang Y. Nickel inhibits urocortin-induced relaxation in the rat pulmonary artery. Eur J Pharmacol 2004; 488: 169-172.
82. Huang Y, Chan FL, Lau CW, et al. Roles of cyclic AMP and Ca2+-activated K+ channels in endothelium-independent relaxation by urocortin in the rat coronary artery. Cardiovasc Res 2003; 57: 824-833.
83. Kageyama K, Furukawa K, Miki I, Terui K, Motomura S, Suda T. Vasodilative effects of urocortin II via protein kinase A and a mitogen-activated protein kinase in rat thoracic aorta. J Cardiovasc Pharmacol 2003; 42: 561-565.
84. Kageyama K, Gaudriault GE, Suda T, Vale WW. Regulation of corticotropin-releasing factor receptor type 2beta mRNA via cyclic AMP pathway in A7r5 aortic smooth muscle cells. Cell Signal 2003; 15: 17-25.
85. Sanz E, Monge L, Fernandez N, et al. Relaxation by urocortin of human saphenous veins. Br J Pharmacol 2002; 136: 90-94.
86. Coste SC, Kesterson RA, Heldwein KA, et al. Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2. Nat Genet 2000; 24: 403-409.
87. Dieterle T, Meili-Butz S, Buhler K, et al. Immediate and sustained blood pressure lowering by urocortin 2: a novel approach to antihypertensive therapy? Hypertension 2009; 53: 739-744.
88. Chen J, Tao J, Zhang R, Xu Y, Soong T, Li S. Urocortin inhibits mesenteric arterial remodeling in spontaneously hypertensive rats. Peptides 2009; 30: 1117-1123.
89. Venkatasubramanian S, Griffiths ME, McLean SG, et al. Vascular effects of urocortins 2 and 3 in healthy volunteers. J Am Heart Assoc 2013; 2: e004267.
90. Yang C, Xu Y, Mendez T, Wang F, Yang Q, Li S. Effects of intravenous urocortin on angiotensin-converting enzyme in rats. Vascul Pharmacol 2006; 44: 238-246.
91. Yang C, Liu X, Li S. Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats. Can J Physiol Pharmacol 2010; 88: 168-176.
92. Squillacioti C, De Luca A, Liguori G, Paino S, Mirabella N. Expression of urocortin and corticotropin-releasing hormone receptors in the bovine adrenal gland. Gen Comp Endocrinol 2011; 172: 416-422.
93. Rademaker MT, Charles CJ, Nicholls MG, Richards AM. Urocortin 2 combined with angiotensin-converting enzyme inhibition in experimental heart failure. Clin Sci (Lond) 2008; 114: 635-642.
94. Rademaker MT, Charles CJ, Espiner EA, Frampton CM, Lainchbury JG, Richards AM. Endogenous urocortins reduce vascular tone and renin-aldosterone/endothelin activity in experimental heart failure. Eur Heart J 2005; 26: 2046-2054.
95. Nemoto T, Mano-Otagiri A, Shibasaki T. Urocortin 2 induces tyrosine hydroxylase phosphorylation in PC12 cells. Biochem Biophys Res Commun 2005; 330: 821-831.
96. Dermitzaki E, Tsatsanis C, Minas V, et al. Corticotropinreleasing factor (CRF) and the urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type-specific manner. Endocrinology 2007; 148: 1524-1538.
97. Chu CP, Qiu DL, Kato K, et al. Central stresscopin modulates cardiovascular function through the adrenal medulla in conscious rats. Regul Pept 2004; 119: 53-59.
98. Yokotani K, Murakami Y, Okada S, Hirata M. Role of brain arachidonic acid cascade on central CRF1 receptor-mediated activation of sympatho-adrenomedullary outflow in rats. Eur J Pharmacol 2001; 419: 183-189.
99. Jin R, Li MZ, Bing YH, et al. Intracerebroventricular injection of stresscopin-related peptide enhances cardiovascular function in conscious rats. Regul Pept 2013; 186: 7-11.
100. Charles CJ, Jardine DL, Nicholls MG, Rademaker MT, Richards AM. Urocortin 1 exhibits potent inhibition of cardiac sympathetic nerve activity in conscious sheep. J Hypertens 2008; 26: 53-60.
101. Charles CJ, Jardine DL, Rademaker MT, Richards AM. Urocortin 3 inhibits cardiac sympathetic nerve activity in conscious sheep. J Cardiovasc Pharmacol 2011; 58: 418-423.
102. Charles CJ, Jardine DL, Rademaker MT, Richards AM. Urocortin 2 induces potent long-lasting inhibition of cardiac sympathetic drive despite baroreflex activation in conscious sheep. J Endocrinol 2010; 204: 181-189.
103. Honjo T, Inoue N, Shiraki R, et al. Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin. J Vasc Res 2006; 43: 131-138.
104. Agnello D, Bertini R, Sacco S, Meazza C, Villa P, Ghezzi P. Corticosteroid-independent inhibition of tumor necrosis factor production by the neuropeptide urocortin. Am J Physiol 1998; 275: E757-E762.
105. Yang C, Xu Y, Li S. Urocortin: a beneficial or detrimental agent to endothelium? Biochem Biophys Res Commun 2008; 371: 345-349.
106. Singh LK, Boucher W, Pang X, et al. Potent mast cell degranulation and vascular permeability triggered by urocortin through activation of corticotropin-releasing hormone receptors. J Pharmacol Exp Ther 1999; 288: 1349-1356.
107. Wu Y, Hu J, Zhang R, et al. Enhanced intracellular calcium induced by urocortin is involved in degranulation of rat lung mast cells. Cell Physiol Biochem 2008; 21: 173-182.
108. Xu Y, Zhang R, Chen J, et al. Urocortin promotes the development of vasculitis in a rat model of thromboangiitis obliterans via corticotrophin-releasing factor type 1 receptors. Br J Pharmacol 2009; 157: 1368-1379.
109. Zhang R, Xu Y, Fu H, Wang J, Jin L, Li S. Urocortin induced expression of COX-2 and ICAM-1 via corticotrophin-releasing factor type 2 receptor in rat aortic endothelial cells. Br J Pharmacol 2009; 158: 819-829.
110. Wu Y, Zhang R, Zhou C, et al. Enhanced expression of vascular cell adhesion molecule-1 by corticotrophinreleasing hormone contributes to progression of atherosclerosis in LDL receptor-deficient mice. Atherosclerosis 2009; 203: 360-370.
111. Emeto TI, Moxon JV, Biros E, et al. Urocortin 2 is associated with abdominal aortic aneurysm and mediates anti-proliferative effects on vascular smooth muscle cells via corticotrophin releasing factor receptor 2. Clin Sci (Lond) 2014; 126: 517-527.
112. Rush C, Nyara M, Moxon JV, Trollope A, Cullen B, Golledge J. Whole genome expression analysis within the angiotensin II-apolipoprotein E deficient mouse model of abdominal aortic aneurysm. BMC Genomics 2009; 10: 298.
113. Hao Z, Huang Y, Cleman J, et al. Urocortin2 inhibits tumor growth via effects on vascularization and cell proliferation. Proc Natl Acad Sci USA 2008; 105: 3939-3944.
114. Wang J, Jin L, Chen J, Li S. Activation of corticotropinreleasing factor receptor 2 inhibits the growth of human small cell lung carcinoma cells. Cancer Invest 2010; 28: 146-155.
115. Scarabelli TM, Pasini E, Stephanou A, et al. Urocortin promotes hemodynamic and bioenergetic recovery and improves cell survival in the isolated rat heart exposed to ischemia/reperfusion. J Am Coll Cardiol 2002; 40: 155-161.
116. Calderon-Sanchez EM, Ruiz-Hurtado G, Smani T, et al. Cardioprotective action of urocortin in postconditioning involves recovery of intracellular calcium handling. Cell Calcium 2011; 50: 84-90.
117. Chanalaris A, Lawrence KM, Stephanou A, et al. Protective effects of the urocortin homologues stresscopin (SCP) and stresscopin-related peptide (SRP) against hypoxia/reoxygenation injury in rat neonatal cardiomyocytes. J Mol Cell Cardiol 2003; 35: 1295-1305.
118. Brar BK, Jonassen AK, Stephanou A, et al. Urocortin protects against ischemic and reperfusion injury via a MAPKdependent pathway. J Biol Chem 2000; 275: 8508-8514.
119. Brar BK, Stephanou A, Knight R, Latchman DS. Activation of protein kinase B/Akt by urocortin is essential for its ability to protect cardiac cells against hypoxia/reoxygenation-induced cell death. J Mol Cell Cardiol 2002; 34: 483-492.
120. Schulman D, Latchman DS, Yellon DM. Urocortin protects the heart from reperfusion injury via upregulation of p42/p44 MAPK signaling pathway. Am J Physiol Heart Circ Physiol 2002; 283: H1481-H1488.
121. Brar BK, Railson J, Stephanou A, Knight RA, Latchman DS. Urocortin increases the expression of heat shock protein 90 in rat cardiac myocytes in a MEK1/2-dependent manner. J Endocrinol 2002; 172: 283-293.
122. Gordon JM, Dusting GJ, Woodman OL, Ritchie RH. Cardioprotective action of CRF peptide urocortin against simulated ischemia in adult rat cardiomyocytes. Am J Physiol Heart Circ Physiol 2003; 284: H330-H336.
123. Lawrence KM, Kabir AM, Bellahcene M, et al. Cardioprotection mediated by urocortin is dependent on PKCepsilon activation. FASEB J 2005; 19: 831-833.
124. Lawrence KM, Chanalaris A, Scarabelli T, et al. K(ATP) channel gene expression is induced by urocortin and mediates its cardioprotective effect. Circulation 2002; 106: 1556-1562.
125. Townsend PA, Davidson SM, Clarke SJ, et al. Urocortin prevents mitochondrial permeability transition in response to reperfusion injury indirectly by reducing oxidative stress. Am J Physiol Heart Circ Physiol 2007; 293: H928-H938.
126. Liu CN, Yang C, Liu XY, Li S. In vivo protective effects of urocortin on ischemia-reperfusion injury in rat heart via free radical mechanisms. Can J Physiol Pharmacol 2005; 83: 459-465.
127. Barry SP, Lawrence KM, McCormick J, et al. New targets of urocortin-mediated cardioprotection. J Mol Endocrinol 2010; 45: 69-85.
128. Lawrence KM, Scarabelli TM, Turtle L, et al. Urocortin protects cardiac myocytes from ischemia/reperfusion injury by attenuating calcium-insensitive phospholipase A2 gene expression. FASEB J 2003; 17: 2313-2315.
129. Takatani-Nakase T, Takahashi K. Cardioprotective activity of urocortin by preventing caspase-independent, nonapoptotic death in cultured neonatal rat cardiomyocytes exposed to ischemia. Biochem Biophys Res Commun 2010; 402: 216-221.
130. Yuan Z, McCauley R, Chen-Scarabelli C, et al. Activation of Src protein tyrosine kinase plays an essential role in urocortin-mediated cardioprotection. Mol Cell Endocrinol 2010; 325: 1-7.
131. Chen-Scarabelli C, Saravolatz Ii L, McCaukey R, et al. The cardioprotective effects of urocortin are mediated via activation of the Src tyrosine kinase-STAT3 pathway. JAKSTAT 2013; 2: e24812.
132. Janjua S, Lawrence KM, Ng LL, Latchman DS. The cardioprotective agent urocortin induces expression of CT- 1 Cardiovasc Toxicol 2003; 3: 255-262.
133. Cong B, Zhu X, Cao B, Xiao J, Wang Z, Ni X. Estrogens protect myocardium against ischemia/reperfusion insult by up-regulation of CRH receptor type 2 in female rats. Int J Cardiol 2013; 168: 4755-4760.
134. Cong B, Xu Y, Sheng H, et al. Cardioprotection of 17betaestradiol against hypoxia/reoxygenation in cardiomyocytes is partly through up-regulation of CRH receptor type 2. Mol Cell Endocrinol 2014; 382: 17-25.
135. Cserepes B, Jancso G, Gasz B, et al. Cardioprotective action of urocortin in early pre- and postconditioning. Ann NY Acad Sci 2007; 1095: 228-239.
136. Ng LL, Loke IW, O'Brien RJ, Squire IB, Davies JE. Plasma urocortin in human systolic heart failure. Clin Sci (Lond) 2004; 106: 383-388.
137. Davis ME, Pemberton CJ, Yandle TG, et al. Urocortin-1 infusion in normal humans. J Clin Endocrinol Metab 2004; 89: 1402-1409.
138. Huang Y, Yao XQ, Lau CW, Chan YC, Tsang SY, Chan FL. Urocortin and cardiovascular protection. Acta Pharmacol Sin 2004; 25: 257-265.
139. Siennicka A, Drozdzynska M, Chelstowski K, Cnotliwy M, Jastrzebska M. Haemostatic factors and intraluminal thrombus thickness in abdominal aortic aneurysm. Is secondary fibrinolysis relevant? J Physiol Pharmacol 2013; 64: 321-330.
140. Gnus J, Czerski A, Ferenc S, et al. In vitro study on the effects of some selected agonists and antagonists of alpha(1)-adrenergic receptors on the contractility of the aneurysmally-changed aortic smooth muscle in humans. J Physiol Pharmacol 2012; 63: 29-34.
141. Chen-Scarabelli C, Faggian G, Yuan Z, et al. Warm-blood cardioplegic arrest induces selective mitochondrial translocation of protein kinase Cepsilon followed by interaction with 6.1 inwardly rectifying potassium channel subunit in viable myocytes overexpressing urocortin. J Thorac Cardiovasc Surg 2009; 138: 1213-1221.
142. Scarabelli TM, Pasini E, Ferrari G, et al. Warm blood cardioplegic arrest induces mitochondrial-mediated cardiomyocyte apoptosis associated with increased urocortin expression in viable cells. J Thorac Cardiovasc Surg 2004; 128: 364-371.
143. Wright SP, Doughty RN, Frampton CM, Gamble GD, Yandle TG, Richards AM. Plasma urocortin 1 in human heart failure. Circ Heart Fail 2009; 2: 465-471.
144. Topal E, Yagmur J, Otlu B, et al. Relationship of urocortin- 2 with systolic and diastolic functions and coronary artery disease: an observational study. Anadolu Kardiyol Derg 2012; 12: 115-120.
145. Yildirim E, Keles I, Cakmak HA, Cosansu K, Can G, Ikitimur B. Evaluation of the clinical utility of urocortin 1 in systolic heart failure. Kardiol Pol 2014; 72: 452-458.
146. Davis ME, Pemberton CJ, Yandle TG, et al. Urocortin 2 infusion in healthy humans: hemodynamic, neurohormonal, and renal responses. J Am Coll Cardiol 2007; 49: 461-471.
147. Davis ME, Pemberton CJ, Yandle TG, et al. Effect of urocortin 1 infusion in humans with stable congestive cardiac failure. Clin Sci (Lond) 2005; 109: 381-388.
148. Gheorghiade M, Greene SJ, Ponikowski P, et al. Haemodynamic effects, safety, and pharmacokinetics of human stresscopin in heart failure with reduced ejection fraction. Eur J Heart Fail 2013; 15: 679-689.
149. Pal K, Swaminathan K, Xu HE, Pioszak AA. Structural basis for hormone recognition by the human CRFR2(alpha) G protein-coupled receptor. J Biol Chem 2010; 285: 40351- 40361.
150. Thompson JD, Gibson TJ, Higgins DG. Multiple sequence alignment using ClustalW and ClustalX. Curr Protoc Bioinformatics 2002; Chapter 2: Unit 2 3.
151. Gouet P, Robert X, Courcelle E. ESPript/ENDscript: Extracting and rendering sequence and 3D information from atomic structures of proteins. Nucleic Acids Res 2003; 31: 3320-3323.