The potentiating effects of phorbol ester on ACTH-, cholera toxin-, and forskolin-induced cAMP production by cultured bovine adrenal cells is not mediated by the inactivation of alpha subunit of Gi protein.

Phorbol ester (PMA) potentiates ACTH-induced cAMP production by both fresh isolated and 7-day-old cultured adrenal cells, but the effect on cultured cells was greater than in fresh cells. In cultured cells the potentiating effects of PMA were dose-dependent and were observed at each effective dose of ACTH without modification of the ED50 for this hormone. These effects of PMA do not seem to be exerted through a modification of the alpha subunit of Gi since pretreatment of the cells with Bordetella pertussis toxin did not modify the action of PMA and since the amount of alpha i in 7-day-old cultured cells was ten times lower than in fresh cells, while the potentiating effect was lower in the latter. Moreover, since PMA still exerted its potentiating action in cells stimulated by maximal concentration of cholera toxin or forskolin either alone or in combination with ACTH, it is likely that its action is not mediated exclusively by the alpha subunit of Gs. Taken together, the present results and those of the literature suggest that this potentiating effect of phorbol ester on effector-induced cAMP production might be mediated by inhibition of the beta-subunit of G proteins.