Differential effects of protein kinase C activators on carbamylcholine- and high K+-induced rises in intracellular free calcium concentration in cultured adrenal chromaffin cells.

Summary Pretreatment of adrenal chromaffin cells with protein kinase C activators, i.e. 12-0-tetradecanoyl phorbol-13-acetate (TPA) and 1-oleoyl 2-acetyl glycerol (OAG), partially inhibited carbamylcholine (CCh)-induced rise in intracellular free Ca 2+ concentration ([Ca 2+ ] i ). The apparent IC50 values of TPA and OAG were 3 nM and 25 μM, respectively. The effect of TPA on the CCh-induced rise in [Ca 2+ ] i was overcome by pretreatment of the cells with a protein kinase C inhibitor, 1-(5-isoquinidinesulfonyl)-2-methylpiperazine hydrochloride (H-7). In cotrast, KC1-induced rise in [Ca 2+ ] i was not affected by pretreating the cells with TPA or OAG. An inactive phorbol ester, 4α-phorbol 12,13-didecanoate failed to affect the CCh-induced rise in [Ca 2+ ] i . CCh-induced 45 Ca 2+ uptake was also partially inhibited by pretreatment of the cells with TPA or OAG, but KC1-induced 45 Ca 2+ uptake was not affected by these pretreatments. These results indicate that protein kinase C activation causes an uncoupling of signal transduction between the nicotinic receptors and Ca 2+ channels.