Diverse effects of Ca 2+ on the prostacyclin and corticotropin modulation of adenosine 3': 5'- monophosphate and steroid production in normal cat and mouse tumor cells of the adrenal cortex

Abstract

Isolated cat adrenocortical cells exposed to corticotropin (ACTH) (2–50 μU) and prostacyclin (PGI 2) (10 −8 to 10 −4M) demonstrated dose- and time-dependent increases in cyclic AMP formation and steroid production. In the absence of extracellular Ca 2+ ACTH (5 μU) did not augment cyclic AMP levels and steroid release. In contrast, Ca 2+ deprivation did not affect the ability of PGI 2 (10 −6M) to augment cyclic AMP levels and only partially depressed PGI 2-induced steroid release, indicating that ACTH and PGI 2 affect the adenylate cyclase-cyclic AMP system differently. The distinctive effects of PGI 2 and ACTH were further demonstrated in mouse adrenal tumor (Y-1) cells, which responded to ACTH and cholera extertoxin (choleragen) (10 −9 M) with increases in cyclic AMP formation and steroidogenesis, whereas PGI 2 elicited a profound decrease in cyclic AMP levels and failed to enhance steroid production. The basis of these characteristic effects of ACTH and PGI 2on normal and adrenal tumor cells appears to be their particular actions on membrane receptors, which modulate cyclic AMP metabolism through different Ca 2+ -mediated mechanisms.