Calcium channels and nifedipine inhibition of serotonin-induced [3H]thymidine incorporation in cultured cerebral smooth muscle cells.
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 microM). 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.
Kent
T A
TA
Department of Neurology, University of Texas Medical Branch, Galveston 77550.
Jazayeri
A
A
Simard
J M
JM
D000818:Animals; D001488:Basilar Artery / Q000166:cytology / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D006168:Guinea Pigs; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism*; D014316:Tritium
D015220:Calcium Channels; D014316:Tritium; D012701:Serotonin; D004247:DNA; D009543:Nifedipine; D013936:Thymidine