Inhibition by dihydropyridines of regulatory volume decrease and osmolyte fluxes in cultured astrocytes is unrelated to extracellular calcium.
The 1,4-dihydropyridines (DHP), nimodipine (NMD) and nitrendipine (NTD) were potent blockers of regulatory volume decrease (RVD) and the volume-associated release of [3H]taurine and chloride (measured as 125I) in 2-weeks cultured rat cerebellar astrocytes. The IC50 were 30 microM and 29 microM for taurine efflux and 26 and 27 microM for C1 efflux for NMD and NTD, respectively. Inhibition by DHP was independent of extracellular Ca, as the effect was the same in media with 1 mM Ca or without Ca and 0.5 mM EGTA. DHP did not affect the basal (isosmotic) release of [3H]taurine or 125I inhibition by DHP (measured only on [3H]taurine efflux) was the same in 3-4 weeks cultured cerebellar astrocytes, 2-4 weeks cultured cortical astrocytes and 2-weeks cultured cerebellar astrocytes treated with dibutyril cAMP. Diltiazem (50 microM) and verapamil (100 microM) failed to inhibit RVD or osmolyte efflux.
D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009553:Nimodipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013654:Taurine / Q000378:metabolism; D014882:Water-Electrolyte Balance
D004095:Dihydropyridines; D013654:Taurine; D009553:Nimodipine; D009568:Nitrendipine; D002118:Calcium