Inhibition of High K^+ -Induced Contraction by the ROCKs Inhibitor Y-27632 in Vascular Smooth Muscle : Possible Involvement of ROCKs in a Signal Transduction Pathway
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概要
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In the isolated rat aorta, a ROCKs (rhoA-dependent coiled coil serine/threonine kinases) inhibitor, Y-27632, inhibited the contractions induced not only by receptor agonists but also by high K+ with the similar IC50 values (0.8 – 4.9 μM). However, Y-27632 did not inhibit the increment of cytosolic Ca2+ concentration ([Ca2+]i) due to these stimulants. The Y-27632-induced inhibition of contraction was accompanied by an inhibition of myocin light chain (MLC) phosphorylation, although inhibition of contraction was stronger than that of MLC phosphorylation during the initial phase of contraction. Y-27632 had no effect on the myocin light chain kinase (MLCK) activity. This inhibitor also did not directly change the phosphatase activity. These results suggest that Y-27632 is a selective inhibitor of ROCKs with no direct inhibitory effect on [Ca2+]i, calmodulin, MLCK, or phosphatase. Y-27632 disrupted the actin filament network and decreased the filamentous actin, implying that the stronger inhibition by Y-27632 on early phase of contraction than MLC phosphorylation may be explained by this effect. These results suggest that the high K+-induced MLC phosphorylation and contraction are mediated not only by the classical Ca2+/calmodulin-dependent MLCK system but also by a novel MLC phosphorylation pathway involving ROCKs. One of the possibilities is that high K+ activates ROCKs to inhibit myosin phosphatase resulting in an augmentation of MLC phosphorylation and contraction.
- 2003-05-01
著者
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Hori Masatoshi
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University
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Ozaki Hiroshi
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University
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Hori Masatoshi
Department Of Radiology Graduate School Of Medicine Osaka University
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Hori M
Leaf Tobacco Research Center Japan Tobacco Inc.:(present Address)laboratory Of Insect Science And Bi
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KARAKI Hideaki
Department of Veterinary Pharmacology, Graduate School of Agricultural and Life Sciences, The Univer
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OKA Tatsuya
Department of Pharmacology, Faculty of Pharmacy, Meijo University
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Ozaki H
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences University Of
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Ozaki Hiroshi
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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SAKAMOTO Kazuyuki
Department of Physics, Graduate School of Science, Tohoku University
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KOHAMA Kazuhiro
Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine
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Kobayashi Haruo
Department Of Veterinary Medicine Faculty Of Agriculture Iwate University
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Hori M
Division Of Veterinary Pharmacology Nippon Veterinary And Animal Science University
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Oka T
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Sato Koichi
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Kohama K
Department Of Pharmacology Gunma University School Of Medicine
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Kohama Kazuhiro
Department Of Molecular And Cellular Pharmacology Faculty Of Medicine Gunma University Graduate Scho
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Karaki Hideaki
Department Of Veterinary Medicine Faculty Of Agriculture Iwate University
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IZUMI Masanori
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The Univers
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Hori Masatoshi
Division Of Veterinary Pharmacology Nippon Veterinary And Animal Science University
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Izumi Masanori
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Sakamoto Kazuyuki
Department Of Material Physics Faculty Of Engineering Science Osaka University
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Karaki Hideaki
Department Of Veterinary Pharmacology Graduate School Of Agricultural And Life Sciences The Universi
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Ozaki Hiroshi
Department Of Electronic Engineering Faculty Of Engineering Osaka University
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Ozaki Hiroshi
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Karaki Hideaki
Department of Veterinary Medical Sciences, Faculty of Agriculture, The University of Tokyo
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