Blockade of DNA synthesis induced by platelet-derived growth factor by tranilast, an inhibitor of calcium entry, in vascular smooth muscle cells

Lin Nie, Hideo Mogami, Makoto Kanzaki, Hiroshi Shibata, Itaru Kojima

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

The present study was conducted to establish a pharmacological method of controlling growth of vascular smooth muscle cells (VSMC) by blocking calcium entry. In cultured rat VSMC, 1 nM platelet-derived growth factor (PDGF) induced a biphasic elevation of cytoplasmic free calcium concentration, ([Ca2+](c)). The second sustained phase of [Ca2+](c) was dependent on extracellular calcium. At lower concentrations, PDGF induced oscillatory changes in [Ca2+](c), and reduction of extracellular calcium attenuated the oscillation. An antiallergic compound, tranilast, abolished the sustained phase of [Ca2+](c) induced by 1 nM PDGF. Tranilast also inhibited the oscillatory changes in [Ca2+](c) induced by 200 pM PDGF. In addition, PDGF- induced calcium influx in the late G1 phase, as assessed by measuring the initial uptake of 45Ca, was inhibited by tranilast in a concentration- dependent manner. Tranilast also inhibited PDGF-augmented DNA synthesis; the ID50 for the inhibition of DNA synthesis was nearly identical to that for calcium influx. Although tranilast blocked PDGF-induced calcium entry, it did not affect PDGF-mediated autophosphorylation of the PDGF receptor, activation of phosphatidylinositol 3-kinase, activation of Ras or mitogen-activated protein kinase. Similarly, PDGF-induced elevation of diacylglycerol was not affected by tranilast. These results suggest that the antiallergic drug tranilast inhibits PDGF-induced DNA synthesis by blocking PDGF-mediated calcium entry. Tranilast may be of use in controlling PDGF-induced DNA synthesis in VSMC.

Original languageEnglish
Pages (from-to)763-769
Number of pages7
JournalMolecular pharmacology
Volume50
Issue number4
Publication statusPublished - 1996 Oct 1
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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