Effects of nicardipine and chlorpromazine on proliferation and intracellular calmodulin in cultured aortic smooth muscle cells

Effects of Ca2+ and calcium antagonists nicardipine (Nic) and chlorpromazine (CPZ) on the proliferation, DNA synthesis and intracellular calmodulin (CaM) levels in cultured rabbit aortic smooth muscle cells were investigated. Maximal response of cell to Ca2+ stimulation occurred in the normal medium with CaCl2 1.4 mmol/L, whereas CaCl2 0.02-0.6 mmol/L, Nic (2.5-40.0 mumol/L) and CPZ (5.0-20.0 mumol/L) inhibited the cell proliferation in a concentration-dependent manner. The additive effects of Nic and CPZ were observed. There was a transient surge of intracellular soluble CaM level at 9h in late G1 phase of the cell cycle just before the initiation of DNA synthesis. Not only the initiation of DNA synthesis but also the CaM surge were prevented by adding Nic or CPZ (20-40 mumol/L) to media. These results suggest that an appropriate extracellular Ca2+ concentration was required for aortic smooth muscle cells to grow normally. Since calcium antagonists influenced the intracellular Ca2+ pool by blockade of calcium channel and they inhibited the CaM function directly by anticalmodulin activity or indirectly through altered intracellular Ca2+ metabolism, intracellular Ca2+ and CaM levels may be involved in the effects of Nic and CPZ on the proliferation and DNA synthesis.