Calcium channels and nifedipine inhibition of serotonin-induced [3H]thymidine incorporation in cultured cerebral smooth muscle cells

Thomas A. Kent, Allahyar Jazayeri, J. Marc Simard

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Cultures of smooth muscle cells were prepared from the basilar artery of adult guinea pigs. Passaged cultures (10-30 passages) that expressed serotonin receptors were studied using [3H]thymidine incorporation. When tested in quiescent medium, serotonin potently stimulated [3H]thymidine incorporation (EC50 of 31 nM) by as much as 400% at 24 h. The number of cells was not significantly increased at 24 or 48 h. At concentrations of 10-8-10-5 M 5-HT, [3H]thymidine uptake was reduced 40-50% by the dihydropyridine Ca2+ channel blocker, nifedipine (1 μM). To demonstrate a possible mechanism for the sensitivity to nifedipine, Ca2+ currents were measured using the whole cell patch clamp technique. The cells expressed dihydropyridine-sensitive L-type Ca2+ channels, but not other subtypes of Ca2+ channels, as indicated by the kinetic and voltage-dependent characteristics of the current and by the stimulatory effect of Bay K 8644. The magnitude of the Ca2+ currents was related exponentially to the membrane surface area, measured as cell capacitance. These data support the association of dihydropyridine-sensitive Ca2+ channels with mitogenesis in vascular smooth muscle, and suggest an alternate mechanism of action for the beneficial effect of dihydropyridines in prophylaxis of cerebral vasospasm.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume12
Issue number1
DOIs
StatePublished - 1992

Keywords

  • Basilar artery
  • Ca channels
  • Cerebral vasospasm
  • Cultured smooth muscle cells
  • Growth factor
  • Nifedipine
  • Serotonin
  • [H]thymidine

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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