Inhibition of calcium flux and calcium channel antagonist binding in the PC12 neural cell line by phorbol esters and protein kinase C.
Ca2+- and phospholipid-dependent protein kinase (protein kinase C) has been shown to modify receptor-mediated Ca2+ responses in a variety of cells. To assess its possible role in modulating voltage-dependent Ca2+ responses, we examined the effect of tumor-promoting phorbol esters, which activate protein kinase C, on Ca2+ channel function in the PC12 neural cell line. Phorbol 12-myristate 13-acetate reduced K+-depolarization-evoked 45Ca uptake and decreased binding of the Ca2+ channel antagonist [3H] (+)PN200-110 to intact cells. Inhibition of binding was markedly reduced in PC12 membranes, but was restored by reconstituting membranes with protein kinase C activity. Protein kinase C may therefore participate in endogenous regulation of voltage-dependent Ca2+ channels in mammalian neural cells.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D017275:Isradipine; D051379:Mice; D009432:Neural Crest / Q000187:drug effects / Q000378:metabolism*; D010069:Oxadiazoles / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004075:Diglycerides; D010069:Oxadiazoles; D010703:Phorbol Esters; D010704:Phorbols; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium; C033085:phorbol; D017275:Isradipine; C013965:diolein