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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 ([Ca²⁺]_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 [Ca²⁺]_i, and further identified a transient PKC-independent component of secretion dependent upon Ca²⁺ release from intracellular stores, whereas sustained secretion required entry of extracellular Ca²⁺. Interactions among carbachol, PKC inhibitors, phorbol 12-myristate 13-acetate, and thapsigargin to modulate [Ca²⁺]_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 [Ca²⁺]_i levels to activate cPKCs in mediating sustained muscarinic-induced secretion.

Keywords

salivary glands muscarinic cholinergic receptors protein kinase C mucous cells exocrine secretion stimulus-secretion coupling

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Role of Calcium and PKC in Salivary Mucous Cell Exocrine Secretion

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