Role of calcium and PKC in salivary mucous cell exocrine secretion

Fluid and exocrine secretion of mucins by salivary mucous glands is regulated predominantly by parasympathetic activation of muscarinic receptors. a direct role for subsequent putative signaling steps,phospholipase c (plc),increased intracellular calcium ([ca 2+]i),and isoforms of protein kinase c (pkc) in mediating muscarinic exocrine secretion has not been elucidated,and these are potential therapeutic targets to enhance mucin secretion in hyposalivary patients. we found that muscarinic-induced mucin secretion by rat sublingual tubulo-acini was dependent upon plc activation and the subsequent increase in [ca 2+]i,and further identified a transient pkc-independent component of secretion dependent upon ca 2+ release from intracellular stores,whereas sustained secretion required entry of extracellular ca 2+. interactions among carbachol,pkc inhibitors,phorbol 12-myristate 13-acetate,and thapsigargin to modulate [ca 2+]i implicated conventional pkc isoforms in mediating sustained secretion. with increasing times during carbachol perfusion of glands,in situ,pkc-? redistributed across glandular membrane compartments and underwent a rapid and persistent accumulation near the luminal borders of mucous cells. pkc-?1 displayed transient localization near luminal borders,whereas the novel pkcs,pkc-ω or pkc-α,displayed little or no redistribution in mucous cells. collective results implicate synergistic interactions between diacylglycerol (dag) and increasing [ca 2+]i levels to activate cpkcs in mediating sustained muscarinic-induced secretion. © 2011 international & american associations for dental research.