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

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Author(s)

Abstract

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 Ca<SUP>2+</SUP> influx; the concentration for the inhibition of Ca<SUP>2+</SUP> influx was nearly identical to that for inhibition of VSMC proliferation. The Ca<SUP>2+</SUP> influx induced by PDGF was also attenuated by NiCl<SUB>2</SUB> but not by nifedipine, suggesting that PDGF-induced Ca<SUP>2+</SUP> 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 Ca<SUP>2+</SUP> influx and downstream signals such as the Ca<SUP>2+</SUP>/PKC signaling pathway, leading to AP-1 induction.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 84(3), 252-258, 2000-11-01

    The Japanese Pharmacological Society

References:  31

Codes

  • NII Article ID (NAID)
    10008186020
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    5586778
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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