Muscarinic Type 3 Receptor Induces Cytoprotective Signaling in Salivary Gland Cells through Epidermal Growth Factor Receptor Transactivation

摘要: Muscarinic type 3 receptor (M3R) plays a pivotal role in the induction of glandular fluid secretions. Although M3R is often target autoantibodies Sjogren's syndrome (SjS), chemical agonists for are clinically used to stimulate saliva secretion patients with SjS. Aside from its activity promoting secretion, however, it unclear whether activation related other biological events This study aimed investigate cytoprotective effect agonist-mediated on apoptosis induced human salivary gland (HSG) cells. Carbachol (CCh), muscarinic receptor-specific agonist, abrogated tumor necrosis factor α/interferon γ-induced through pathways involving caspase 3/7, but was decreased by antagonist, mitogen-activated protein kinase kinase/extracellular signal-regulated (ERK) inhibitor, phosphatidylinositol 3-kinase/Akt or an epidermal growth (EGFR) inhibitor. Ligation CCh transactivated EGFR and phosphorylated ERK Akt, downstream targets EGFR. Inhibition intracellular calcium release C δ, both which involved cell signaling M3R-mediated did not affect CCh-induced Akt phosphorylation. stimulated Src phosphorylation binding A inhibitor attenuated CCh/M3R-induced transactivation cascades. Overall, these results indicated that CCh/M3R leading phosphorylation, turn suppressed 3/7-mediated apoptotic signals HSG study, first time, proposes CCh-mediated can promote only also survival cells inflammatory context