Mechanism of Human Urotensin II-Induced Contraction in Rat Aorta

Journal of Pharmacological Sciences

Hideaki Karaki¹  Hiroshi Ozaki¹  Masatoshi Hori¹  Ichiro Wakabayashi²  Katsunari Tasaki² 

[1] Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo;Department of Hygiene & Preventive Medicine, School of Medicine, Yamagata University

关键词: urotensin II;    rat aorta;    Ca2+;    myosin phosphorylation;    Ca2+ sensitization;   

DOI  :  10.1254/jphs.94.376

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(29)Cited-By(19)Urotensin II induced sustained contraction with an EC50 value of 2.29 ± 0.12 nM in rat aorta. Urotensin II (100 nM) transiently increased cytosolic Ca2+ level ([Ca2+]i), followed by a small sustained phase superimposed with rhythmic oscillatory change. In the presence of verapamil and La3+, the [Ca2+]i oscillation was completely inhibited, although a small transient increase in [Ca2+]i remained. The urotensin II-induced contraction was also partially inhibited by verapamil and La3+. Combined application of verapamil, La3+, and thapsigargin completely inhibited the increase in [Ca2+]i with only partial inhibition of the contraction elicited by urotensin II. Urotensin II increased myosin light chain (MLC) phosphorylation to a level greater than that induced by 72.7 mM KCl (high K+). Pretreatment with Go6983 (PKC inhibitor), U0126 (MEK inhibitor), or SB203580 (p38MARK inhibitor) partially inhibited the urotensin II-induced contraction with no effects on the high K+-induced contractions. Wortmannin (MLC kinase inhibitor) only partially inhibited urotensin II-induced contraction, although it completely inhibited the high K+-induced contraction. These results suggest that urotensin II-induced contraction is mediated by the Ca2+/calmodulin/MLC kinase system and modulated by the Ca2+ sensitization mechanisms to increase MLC phosphorylation. In addition, activations of PKC, p38MAPK, and ERK1/2 modulate the contractility mediated by urotensin II in rat aorta.

【 授权许可】

Unknown