ENDOTHELIN-1 STIMULATES SODIUM-DEPENDENT CALCIUM EFFLUX FROM BOVINE ADRENAL CHROMAFFIN CELLS IN CULTURE

I The effect of endothelin (ET)-1 on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. ET-1 (10(-7) M) significantly i ncreased intracellular free Ca2+ level ([Ca2+](i)), Ca-45(2+) uptake a nd catecholamine secretion in the cells. 2. ET-1 stimulated the efflux of Ca-45(2+) from the cells preloaded with Ca-45(2+) in a concentrati on-dependent manner (10(-9)-10(-7) M). This stimulatory effect was inh ibited by ETB receptor antagonist BQ788, but not by ETA receptor antag onist BQ123. Selective ETB receptor agonists Suc-[Glu(9), Ala(11,15)]- ET-1 and sarafotoxin S6c (SRTX) also stimulated Ca-45(2+) efflux from the cells. 3 ET-1, Suc-[Glu(9), Ala(11,15)]-ET-1 and SRTX increased th e 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 Ca-45(2+) efflux were in hibited by N-G-monomethyl-L-arginine acetate (L-NMMA), a competitive i nhibitor of NO synthase. 4 The Ca-45(2+) efflux stimulated by ET-1 was inhibited by deprivation of extracellular Na+, but not by deprivation of Ca2+. 5 These results suggest that ET-1 stimulates an extracellula r Na+-dependent Ca2+ efflux through the activation of NO synthase in c ultured bovine adrenal chromaffin cells.