Regulations by cyclic nucleotides and phorbol ester of calcium efflux from cultured bovine adrenal chromaffin cells

Abstract The effects of cyclic nucleotides and phorbol ester on Ca 2+ efflux from cultured bovine adrenal chromaffin cells were examined. Dibutyryl cyclic AMP (DB-cAMP), forskolin (an activator of adenylate cyclase ), dibutyryl cyclic GMP (DB-cGMP) and nitroprusside (an activator of guanylate cyclase) all stimulated 45 Ca 2+ efflux from the cells preloaded with 45 Ca 2+ . These agents did not increase the intracellular free Ca 2+ ([Ca 2+ ]i) level. On the contrary, phorbol 12-myristate 13-acetate (PMA; an activator of protein kinase C) did not affect the efflux of 45 Ca 2+ , but inhibited the increase in 45 Ca 2+ efflux caused by DB-cAMP, forskolin, DB-cGMP or nitroprusside. The 45 Ca 2+ effluxes stimulated by cyclic nucleotides, forskolin and nitroprusside were inhibited by deprivation of extracellular Na + ([Na + ]o). These results suggest that both cAMP- and cGMP-dependent protein kinases are involved in the stimulatory mechanism of [Na + ]o dependent Ca 2+ efflux, probably through acceleration of [Na + ]o [Ca 2+ ]i exchange and that protein kinase C plays an inhibitory role in this mechanism.