Nicardipine-sensitive enhancement of high K+ -evoked dopamine release in PC12 cells pretreated with 12-O-tetradecanoylphorbol 13-acetate.

The effects of the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) on stimulus-evoked dopamine release were studied in PC12 cells. Pretreatment of the cells with TPA resulted in an enhancement of dopamine release which could be further stimulated by high concentrations of K+, A23187, but not with carbamylcholine. TPA-dependent, high-K+ -evoked enhancement of dopamine release was studied in detail: a maximum release was observed (169% of control) in response to 50 mM KCl upon treatment with 10(-7) M TPA for 5 min at 37 degrees C. This enhancement of dopamine release was associated with the concomitant reduction of the concentration rise of intracellular Ca2+ ([Ca2+]i) induced by a high concentration of K+ monitored by a fluorescent indicator, fura2. Thus, these data provide an example for alteration in the efficiency of stimulus-secretion coupling as pointed out in our previous paper. Moreover, we have shown that nicardipine, CdCl2, and CoCl2 inhibit high-K+ -evoked dopamine release more effectively in TPA treated cells than that of untreated cells, and that the TPA-dependent, high-K+ -evoked dopamine release observed in TPA treated cells is completely abolished by the presence of nicardipine, Cd2+ or Co2+, but is only partially inhibited in the presence of verapamil. These relevant findings suggest the possible involvement of protein kinase C in regulating the efficiency of a high-K+ -evoked dopamine release through the modification of nicardipine-sensitive Ca2+ channels.