SK&F 96365, a receptor-mediated calcium entry inhibitor, inhibits calcium responses to endothelin-1 in NG108-15 cells.
Endothelin-1 increases intracellular Ca2+ in NG108-15 cells by mobilizing Ca2+ from internal stores and by activating Ca2+ entry through dihydropyridine-sensitive, voltage-gated channels and another, unidentified route. Since SK&F 96365 has recently been reported to inhibit receptor-mediated Ca2+ entry in other systems, we examined its effect on intracellular Ca2+ responses to endothelin-1, measured with the fluorescent Ca2+ indicator fura-2, in NG108-15 cells. SK&F 96365 (30 microM) reduced both dihydropyridine-insensitive (peak) and dihydropyridine-sensitive (plateau) components of intracellular Ca2+ responses to 5 nM endothelin-1. In the presence of 100 nM nimodipine, which blocks dihydropyridine-sensitive channels, SK&F 96365 caused concentration-dependent inhibition of Ca2+ responses to 5 nM endothelin-1, with half-maximal inhibition at 16 microM. These findings support a role for receptor-mediated Ca2+ entry in neurocellular Ca2+ responses to endothelin-1.
Chan
J
J
Department of Neurology, University of California, San Francisco.
Greenberg
D A
DA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D005910:Glioma; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats
D002121:Calcium Channel Blockers; D016232:Endothelins; D007093:Imidazoles; D009553:Nimodipine; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium