TAS-301 Blocks Receptor-Operated Calcium Influx and Inhibits Rat Vascular Smooth Muscle Cell Proliferation Induced by Basic Fibroblast Growth Factor and Platelet-Derived Growth Factor.

• Sasaki Eiji

  Pharmacology Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan

• Nozawa Yoshihisa

  Pharmacology Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan

• Miyoshi Kazuhisa

  Pharmacology Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan

• Kanda Atsuhiro

  Pharmacology Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan

• Yamasaki Yasundo

  Cardiovascular Science Research Laboratory, Hanno Research Center, Taiho Pharmaceutical Co., Ltd., 1-27 Misugidai, Hanno City, Saitama 357-8527, Japan

• Miyake Hidekazu

  Cardiovascular Science Research Laboratory, Hanno Research Center, Taiho Pharmaceutical Co., Ltd., 1-27 Misugidai, Hanno City, Saitama 357-8527, Japan

• Matsuura Naosuke

  Pharmacology Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan

抄録

The purpose of this study was to determine the effect of a recently synthesized durg, TAS-301 [3-bis(4-methoxyphenyl)methylene-2-indolinone], on vascular smooth muscle cell (VSMC) proliferation and the intracellular signal transduction pathways involved in VSMC proliferation. In an in vitro assay, TAS-301 inhibited the proliferation of rat VSMCs stimulated by platelet-derived growth factor (PDGF)-BB, basic fibroblast growth factor, or 2% fetal bovine serum in a concentration-dependent manner. TAS-301 dosedependently inhibited the PDGF-induced Ca²⁺ influx; the concentration for the inhibition of Ca²⁺ influx was nearly identical to that for inhibition of VSMC proliferation. The Ca²⁺ influx induced by PDGF was also attenuated by NiCl₂ but not by nifedipine, suggesting that PDGF-induced Ca²⁺ influx would be mediated by some non-voltage-dependent mechanisms. Furthermore, TAS-301 inhibited PDGF-induced activation of protein kinase C (PKC) and the phorbol 12-myristate 13-acetate-mediated induction of activator protein 1 (AP-1) in a concentration-dependent manner. These findings indicate that TAS-301 inhibited the proliferation of VSMCs by blocking voltage-independent Ca²⁺ influx and downstream signals such as the Ca²⁺/PKC signaling pathway, leading to AP-1 induction.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 84 (3), 252-258, 2000

  公益社団法人 日本薬理学会

キーワード

• TAS-301
• Vascular smooth muscle cell proliferation
• Receptor-operated calcium influx
• Signal transduction

詳細情報

• CRID: 1390001204287857792
• NII論文ID: 10008186020
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.84.252
• COI: 1:CAS:528:DC%2BD3cXosVKiu70%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL書誌ID: 5586778
• PubMed: 11138725
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5586778
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819305049?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819305049?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/84/3/84_3_252/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2001074542
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
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