Endothelin‐1 stimulates sodium‐dependent calcium efflux from bovine adrenal chromaffin cells in culture

1 The effect of endothelin (ET)-1 on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. ET-1 (10−7 M) significantly increased intracellular free Ca2+ level ([Ca2+]i), 45Ca2+ uptake and catecholamine secretion in the cells. 2. ET-1 stimulated the efflux of 45Ca2+ from the cells preloaded with 45Ca2+ in a concentration-dependent manner (10−9–10−7 M). This stimulatory effect was inhibited by ETB receptor antagonist BQ788, but not by ETA receptor antagonist BQ123. Selective ETB receptor agonists Suc-[Glu9, Ala11,15]-ET-1 and sarafotoxin S6c (SRTX) also stimulated 45Ca2+ efflux from the cells. 2 ET-1, Suc-[Glu9, Ala11,15]-ET-1 and SRTX increased the level of cyclic GMP in the adrenal chromaffin cells. ET-1 induced an increase in the nitric oxide (NO) level in the cells. The stimulatory effects by which ET-1 increases NO level and 45Ca2+ efflux were inhibited by NG-monomethyl-L-arginine acetate (L-NMMA), a competitive inhibitor of NO synthase. 3 The 45Ca2+ efflux stimulated by ET-1 was inhibited by deprivation of extracellular Na+, but not by deprivation of Ca2+. 4 These results suggest that ET-1 stimulates an extracellular Na+-dependent Ca2+ efflux through the activation of NO synthase in cultured bovine adrenal chromaffin cells. British Journal of Pharmacology (1998) 125, 55–60; doi:10.1038/sj.bjp.0702047