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A localized cAMP–Ca2+ signaling network in rat parotid acinar cells driven by the TAAR1 agonist RO5256390

Year: 2025

Type: article

Abstract: Trace amine-associated receptor 1 (TAAR1) is highly expressed in rat parotid acinar cells; however, its role in exocrine Ca2+ signaling remains unclear. We herein demonstrated that the selective TAAR1 agonist RO5256390 induced rapid and transient increases in intracellular Ca2+ levels that were completely abolished by the TAAR1 antagonist EPPTB, confirming receptor specificity. Pharmacological dissection revealed dual contributions from extracellular Ca2+ influx via L-type, T-type, and receptor-operated channels and Ca2+ release from intracellular stores mediated by phospholipase C, inositol trisphosphate receptors, and ryanodine receptors. Inhibition of adenylyl cyclase or protein kinase A (PKA) nearly abolished the Ca2+ response, and displacement of PKA from AKAPs using the cell-permeable AKAP-displacing peptide st-Ht31 produced a comparable suppression, underscoring the requirement for microdomain-restricted PKA activity. Exchange protein directly activated by cAMP 2 (Epac 2) and downstream calmodulin-dependent protein kinase II were also indispensable, whereas Epac 1 was dispensable. The present study identified a TAAR1-centered, 3',5'-cyclic adenosine monophosphate microdomain network that co-ordinates Ca2+ entry and release, thereby providing novel targets for the modulation of salivary secretion.

Source: Biomedical Research

DOI: 10.2220/biomedres.46.243