Effects of calcium-antagonists and calmodulin inhibitors on DNA synthesis in cultured rat vascular smooth muscle cells .

Tomita M ; Hirata Y ; Takata S ; Fujita T

Endocrinol Jpn 34 : 313-8 ( 1987)

Abstract
To investigate the role of intracellular Ca2+ in the mechanism of cellular proliferation of vascular smooth muscle cells ( VSMC ) , the effects of Ca2+-antagonists and calmodulin ( CaM ) inhibitors on DNA synthesis stimulated by serum-derived growth factors were studied in cultured VSMCs derived from rat aorta . DNA synthesis assessed by incorporation of [ 3H]thymidine into the cells was significantly stimulated by epidermal growth factor ( EGF ) , platelet-derived growth factor ( PDGF ) or fetal bovine serum ( FBS ) , of which the effects were dose-dependently inhibited by a variety of Ca2+-antagonists , such as verapamil , diltiazem and nicardipine . Trifluoperazine and W-7 , both specific CaM inhibitors , similarly inhibited DNA synthesis stimulated by EGF , PDGF or FBS in a dose-dependent manner , whereas W-5 , a less specific CaM inhibitor , was minimally effective . These data suggest that the Ca2+-CaM system plays an important role in the mechanism of growth factor-induced DNA synthesis in VSMCs .