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.
D000818:Animals; D001921:Brain / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002417:Cattle; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D005260:Female; D005333:Fetus; D020904:Glia Maturation Factor; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D020904:Glia Maturation Factor; D009419:Nerve Tissue Proteins; D013449:Sulfonamides; D014665:Vasodilator Agents; D014268:Trifluoperazine; C017967:W 7