Inhibition by calmodulin antagonists of glioblast DNA synthesis and morphological changes induced by glia maturation factor.

Calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide hydrochlorides (W-7) and trifluoperazine (TFP), markedly inhibited both morphological transforming and mitogenic activities of glia maturation factor (GMF) on rat fetal glioblasts in culture. In the presence of W/-7 (16.5 microM) or TFP (9 microM) the formation of glial processes of glioblasts caused by GMF was decreased, and DNA synthesis (measured by the incorporation of [methyl-3H]thymidine into DNA was inhibited by 50% without changing cell viability. Kinetic analysis of dose-response experiments revealed a noncompetitive fashion of inhibition by W-7 and a mixed fashion by TFP. W-7 appeared to inhibit DNA synthesis at the G1 phase immediately before the beginning of the S phase. The results strongly suggest that calmodulin exerts a significant role on cell multiplication induced by the growth factor.