Difference in Signal Transduction Mechanisms Involved in 5-Hydroxytryptamine- and U46619-Induced Vasoconstrictions

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概要

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• In order to elucidate the signal transduction pathways of vascular smooth muscle contractions induced by stimulation of receptors for 5-hydroxytryptamine (5-HT) and thromboxane A_2 (TXA_2), both of which are released from activated platelets, we examined whether protein kinases, such as tyrosine kinase, p38 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC), are involved in the contraction produced by either 5-HT or U46619 (an analog of TXA_2) in the rat aorta. Both 5-HT and U46619 induced sustained contractions, which were markedly reduced in the absence of extracellular Ca^<2+>. Verapamil (a L-type Ca^<2+> channel blocker) markedly inhibited the contractile response to 5-HT, while the 1146619-induced contraction was only slightly inhibited by verapamil. Both contractile responses to 5-HT and U46619 were significantly inhibited by calphostin C (a PKC inhibitor). On the other hand, both genistein (5 μM, a tyrosine kinase inhibitor) and SB203580 (a p38 MAPK inhibitor) significantly inhibited 5-HT-induced contractions but had little effects on the contractions induced by U46619. These results suggest that the signal transduction mechanisms involved in the contractions mediated via 5-HT and TXA_2 receptors are different as follows. Both the tyrosine kinase and p38 MAPK pathways are involved in 5-HT contraction but not in TXA_2 contraction, while both contractions are strongly dependent on transplasmalemmal Ca^<2+> entry. The contractile responses to both 5-HT and TXA_2 involve voltage-dependent Ca^<2+> channels and PKC.

• 日本平滑筋学会の論文

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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