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

• Tasaki Katsunari

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

• Hori Masatoshi

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

• Ozaki Hiroshi

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

• Karaki Hideaki

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

• Wakabayashi Ichiro

  Department of Hygiene & Preventive Medicine, Yamagata University School of Medicine

抄録

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 A₂ (TXA₂), 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 TXA₂) in the rat aorta. Both 5-HT and U46619 induced sustained contractions, which were markedly reduced in the absence of extracellular Ca²⁺. Verapamil (a L-type Ca²⁺ channel blocker) markedly inhibited the contractile response to 5-HT, while the U46619-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 TXA₂ receptors are different as follows. Both the tyrosine kinase and p38 MAPK pathways are involved in 5-HT contraction but not in TXA₂ contraction, while both contractions are strongly dependent on transplasmalemmal Ca²⁺ entry. The contractile responses to both 5-HT and TXA₂ involve voltage-dependent Ca²⁺ channels and PKC.<br>

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｓｍｏｏｔｈ　Ｍｕｓｃｌｅ　Ｒｅｓｅａｒｃｈ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｓｍｏｏｔｈ　Ｍｕｓｃｌｅ　Ｒｅｓｅａｒｃｈ 39 (5), 107-117, 2003

  日本平滑筋学会

キーワード

• vasoconstriction
• prostaglandins
• signal transduction
• protein kinases
• calcium channels

詳細情報

• CRID: 1390282680034176512
• NII論文ID: 110002912874
• NII書誌ID: AN10364204
• DOI: 10.1540/jsmr.39.107
• ISSN: 18848796
• ISSN: 09168737
• PubMed: 14695024
• Web Site: http://www.jstage.jst.go.jp/article/jsmr/39/5/39_5_107/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2005127904
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可