Protein kinase C differentially inhibits muscarinic receptor operated Ca2+ release and entry in human salivary cells.
We investigated the effects of phorbol myristate acetate on muscarinic receptor-induced Ca2+ release from intracellular stores and extracellular entry in a human salivary duct cell line, HSG-PA. Phorbol myristate acetate (approximately 10(-7) M) blocked both Ca2+ release and Ca2+ entry induced by the muscarinic agonist carbachol. This blockade was the result of the activation of protein kinase C since 4 alpha-phorbol 12,13-didecanoate, which lacks the ability to activate protein kinase C, did not inhibit Ca2+ mobilization responses to carbachol. Importantly, at lower phorbol myristate acetate concentrations (approximately 10(-9) M), carbachol-induced Ca2+ release was blocked, but carbachol-induced Ca2+ entry was maintained. These results show that carbachol-induced Ca2+ entry does not occur via an intracellular store and that protein kinase C plays a role in a feedback control mechanism for muscarinic-induced Ca2+ mobilization at different levels.
He
X J
XJ
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, Bethesda, Maryland 20892.
Wu
X Z
XZ
Baum
B J
BJ
D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010703:Phorbol Esters; D011976:Receptors, Muscarinic; C008876:phorbol-12,13-didecanoate; D002217:Carbachol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium