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.
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D011493:Protein Kinase C / Q000032:analysis; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007473:Ion Channels; D000001:Calcimycin; D002217:Carbachol; D009529:Nicardipine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium; D004298:Dopamine