Mechanism of Human Urotensin II-Induced Contraction in Rat Aorta

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概要

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• 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.

• 社団法人 日本薬理学会の論文
• 2004-04-01

著者

• Hori Masatoshi

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University

• Ozaki Hiroshi

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University

• Hori Masatoshi

  Department Of Radiology Graduate School Of Medicine Osaka University

• Hori M

  Leaf Tobacco Research Center Japan Tobacco Inc.:(present Address)laboratory Of Insect Science And Bi

• TASAKI Katsunari

  Department of Hygiene & Preventive Medicine

• WAKABAYASHI Ichiro

  Department of Hygiene & Preventive Medicine

• Tasaki Katsunari

  Department Of Hygiene & Preventive Medicine

• Tasaki Katsunari

  Department Of Hygiene & Preventive Medicine School Of Medicine Yamagata University

• KARAKI Hideaki

  Department of Veterinary Pharmacology, Graduate School of Agricultural and Life Sciences, The Univer

• Ozaki H

  Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences University Of

• Ozaki Hiroshi

  Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit

• Kobayashi Haruo

  Department Of Veterinary Medicine Faculty Of Agriculture Iwate University

• Wakabayashi Ichiro

  Department Of Environmental And Preventive Medicine Hyogo College Of Medicine

• Wakabayashi Ichiro

  Department Of Hygiene &preventive Medicine Yamagata University School Of Medicine

• Hori M

  Division Of Veterinary Pharmacology Nippon Veterinary And Animal Science University

• Karaki Hideaki

  Department Of Veterinary Medicine Faculty Of Agriculture Iwate University

• Hori Masatoshi

  Division Of Veterinary Pharmacology Nippon Veterinary And Animal Science University

• Karaki Hideaki

  Department Of Veterinary Pharmacology Graduate School Of Agricultural And Life Sciences The Universi

• Ozaki Hiroshi

  Department Of Electronic Engineering Faculty Of Engineering Osaka University

• Ozaki Hiroshi

  Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit

• Karaki Hideaki

  Department of Veterinary Medical Sciences, Faculty of Agriculture, The University of Tokyo

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