Stimulation of calcium entry is prerequisite for DNA synthesis induced by platelet-derived growth factor in vascular smooth muscle cells.

The present study was conducted to determine a role of calcium entry in the growth promoting action of platelet-derived growth factor (PDGF) in cultured rat vascular smooth muscle cells. Addition of PDGF to quiescent cells induced a rapid elevation of cytoplasmic free calcium concentration, [Ca2+]c, followed by a sustained plateau of [Ca2+]c. Removal of extracellular calcium abolished the sustained phase, confirming that PDGF augments calcium entry. When calcium influx rate was determined by measuring initial uptake of [45Ca], PDGF induced a gradual increase in the rate of calcium entry. PDGF-mediated calcium entry became maximal after 90 min of the addition of PDGF, which persisted for at least 8 hrs. Calcium entry induced by PDGF was attenuated by nickel ion but not by a calcium channel blocker, nifedipine. When PDGF-induced calcium entry was blocked for a few hrs by either reducing extracellular calcium or by adding nickel, rate of entrance of S phase was reduced. In particular, VSMC stop progression when calcium entry is blocked in the middle of G1 phase. These results indicate that stimulation of calcium entry is prerequisite for initiation of DNA synthesis induced by PDGF in vascular smooth muscle cells.