Mechanism of urotensin Ⅱ-stimulated adrenomedullin secretion in human vascular endothelial cells

Abstract

Abstract: Objective To study the mechanism of urotensin Ⅱ( UⅡ)-stimulated adrenomedullin secretion in human vascular endothelial cells. Methods In cultured human vascular endothelial cells (HEVCs),different concentrations of UⅡ was used to stimulate the secretion of Adm,and different inhibitors were used to study the changes in the secretion after block of different signal transduction pathways.The contents of Adm in the medium were detected with radioimmunoassay. Results UⅡ-stimulated Adm secretion in the HEVCs in a time- and concentration-dependent manner.Adm contents of the treatment groups were comparable with that of the control group (P<0.05 ),and the secretion of Adm could be inhibited by the inhibitor of extracellular signal-regulated protein kinases (PD098059),p38 kinase inhibitor (SB202190),calmodulin inhibitor (W7) and Ca²⁺ inhibitor (nicardipine)(P<0.05),but calcineurin inhibitor and protein kinase C inhibitor (H7) had no such effect (P>0.05). Conclusion Ca²⁺,MAPK,CaM-PK and p38 signal transduction pathways may play major roles in UⅡ-stimulated cecretion of Adm in HVECs.

CLC Number:

R-33

SHI Xiang-dong¹, LI Zhi-liang¹, WU Hong-chao¹, WANG Tong-han¹, Fu Qiang¹, YAN Quan-neng¹, TANG Chao-shu². Mechanism of urotensin Ⅱ-stimulated adrenomedullin secretion in human vascular endothelial cells[J]. Journal of Southern Medical University, 2005, 25(07): 791-793.

References

[1] Coulouarn Y, Lihrmann I, Jegou S, et al. Cloning of CDNA encoding the urotensin Ⅱ precursor in frog and human reveals intense expression of the urotensin Ⅱ gene in motoneurons of the spinal cord[J]. Proc Natl Acad Sci USA, 1998, 95: 15803-8.
[2] Ames RS, Sarau HM, Chambers JK, et al. Human urotensin Ⅱ is a potent vasoconstrictor and agonist for the orphan receptor GPR 14[J]. Nature, 1999, 401(6750): 282-6.
[3] Watanabe T, Pakala R, Katagiri T, Benedict CR. Synergistic effect of urotensin Ⅱ with serotonin on vascular smooth muscle cell proliferation [J]. J Hypertens, 2001, 19(12): 2191-6.
[4] Watanabe T, Pakala R, Katagiri T, et al. Synergistic effect ofurotensin Ⅱ with mildly oxidized LDL on DNA synthesis in vascular smooth muscle cells [J]. Circulation, 2001, 104(1): 1621-8.
[5] 钟萍,李志樑,吴宏超,等.充血性心力衰竭患者血浆尾加压素Ⅱ变化的临床研究[J].第一军医大学学报,2003,23(2):121-3Zhong P, Li ZL,Wu HC, et al. Clinical study of changes ofurotensin Ⅱ in patients with congestive heart failure [J]. J First Mil Med Univ/Di Yi Jun Yi Da Xue Xue Bao, 2003, 23(2): 121-3.
[6] Kangawa K, Kawamoto M. Adrenomedullin: a novel hypoensive peptide isolated from human pheochromocytoma [J]. Biochem Biophys Res Commun, 1993, 192: 552-60.
[7] 汤健,唐朝枢,陈光慧,等.心血管活性多肽的分子内调控[J] 科技导报,1996,10(10):3-7.
[8] Simard B, Gobeil F Jr, Sirois P, et al. Human urotensin- Ⅱ enhances plasma extravasation in specific vascular districts in Wistar rats [J].Can J Physiol Pharmacol, 2004, 82(1): 16-21.
[9] 袁文俊,李玲,等.尾加压素增加培养心肌细胞c-fos和内皮素-1 mRNA表达[J].心脏杂志,2003,15(1):95.
[10] Sugo S, Minamino N, et al. Effects of vasoactive substances and cAMP related compounds on adrenomedullin production in cultured vascular smooth muscle cells[J]. FEBS Lett, 1995,369(2-3): 311-4.
[11] Cheung BM, Leung R. Plasma concentration of urotensin Ⅱ is raised in hypertension [J]. J Hypertens, 2004, 22(7): 1341-4.
[12] Tsuruda T, Burnett JC. Adrenomedullin: an autocrine/paracrine fac tor for cardiorenal protection[J]. Circ Res, 2002, 90: 625-7.
[13] Niu P, Shindo T. Protective effects of endogenous adrenomedullin on cardiac hypertrophy, fibrosis, and renal damage, Circulation,2004, 109(14): 1789-94..
[14] Gibon A, Conyears S, Bern HA. The influence ofurotensin Ⅱ on calciumflux in the rat aorta [J]. JPharmPharmacol, 1988, 40:893-9.

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