SK&F 96365, a receptor-mediated calcium entry inhibitor, inhibits calcium responses to endothelin-1 in NG108-15 cells

Abstract

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.