title: Role of calcium and PKC in salivary mucous cell exocrine secretion.
abstract: 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-α redistributed across glandular membrane compartments and underwent a rapid and persistent accumulation near the luminal borders of mucous cells. PKC-β1 displayed transient localization near luminal borders, whereas the novel PKCs, PKC-δ or PKC-ε, 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.
authors.affiliation: University of Rochester Medical Center, Center for Oral Biology, Rochester, NY 14642, USA. dculp@dental.ufl.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: Culp
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: R L
authors.initials: RL
authors.lastname: Evans
mesh_terms: D061354:Acinar Cells / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation; D007527:Isoenzymes; D009077:Mucins / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology; D011480:Protease Inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*; D015398:Signal Transduction; D013361:Sublingual Gland / Q000166:cytology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology*
chemical_list: D004075:Diglycerides; D007527:Isoenzymes; D009077:Mucins; D018721:Muscarinic Agonists; D011480:Protease Inhibitors; D011976:Receptors, Muscarinic; C016658:phorbolol myristate acetate; D019284:Thapsigargin; D002217:Carbachol; D011493:Protein Kinase C; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium