Differential effects of Ca2+ channel blockers on Ca2+ transients and cell cycle progression in vascular smooth muscle cells.
We examined the differential effects of Ca2+ channel blockers on the elevation of the cytosolic Ca2+ concentration ([Ca2+]i) and G0/G1 transition induced by platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells in primary culture. The phase of the cell cycle was determined by an immunocytochemical analysis of cell cycle-specific nuclear antigens. [Ca2+]i was monitored by fura-2 microfluorometry. The efficacy of Ca2+ channel blockers for the inhibition of [Ca2+]i elevation induced by PDGF (NiCl2 > isradipine > verapamil = diltiazem) did not parallel that for the inhibition of cell cycle progression induced by PDGF (verapamil = diltiazem > NiCl2 > isradipine). In addition, no significant correlation was observed between the extent of [Ca2+]i elevation and the extent of G0/G1 transition. We thus conclude that the inhibitory effects of Ca2+ channel blockers on the G0)/G1 transition induced by PDGF are not simply due to their inhibitory action on the [Ca2+]i elevations but instead are due to more complex unknown factors.
Ahmed
A
A
Division of Molecular Cardiology, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kobayashi
S
S
Shikasho
T
T
Nishimura
J
J
Kanaide
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010982:Platelet-Derived Growth Factor; C022838:nickel chloride; D009532:Nickel; D014700:Verapamil; D002118:Calcium; D017275:Isradipine