Tumor promoter phorbol myristate acetate inhibits Ca2+ influx through voltage-gated Ca2+ channels in two secretory cell lines, PC12 and RINm5F.
Protein kinase C is known to be involved both in initiation and termination of cellular responses due to phosphoinositide breakdown. Here we report that in PC12 cells (a line of neurosecretory cells derived from a rat pheochromocytoma), pretreatment with nanomolar concentrations of phorbol myristate acetate, PMA, which is believed to specifically activate protein kinase C, inhibits the cytosolic-free Ca2+ concentration rise induced by depolarizing agents. In contrast, plasma membrane potential and 45Ca efflux from preloaded cells were unaffected by PMA pretreatment. Inhibition by PMA and diacylglycerol of the cytosolic-free Ca2+ concentration rise induced by depolarization was observed also in another cell line, the insulin secreting line RINm5F. These results raise the possibility that the voltage-gated Ca2+ channel is under inhibitory control by protein kinase C.
Di Virgilio
F
F
Pozzan
T
T
Wollheim
C B
CB
Vicentini
L M
LM
Meldolesi
J
J
D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D010673:Pheochromocytoma / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D007473:Ion Channels; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium