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Biochem Pharmacol ; 225: 116279, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38740221

ABSTRACT

Berberine, a natural isoquinoline alkaloid, exhibits a variety of pharmacological effects, but the pharmacological targets and mechanisms remain elusive. Here, we report a novel finding that berberine inhibits acetylcholine (ACh)-induced intracellular Ca2+ oscillations, mediated through an inhibition of the muscarinic subtype 3 (M3) receptor. Patch-clamp recordings and confocal Ca2+ imaging were applied to acute dissociated pancreatic acinar cells prepared from CD1 mice to examine the effects of berberine on ACh-induced Ca2+ oscillations. Whole-cell patch-clamp recordings showed that berberine (from 0.1 to 10 µM) reduced ACh-induced Ca2+ oscillations in a concentration-dependent manner, and this inhibition also depended on ACh concentrations. The inhibitory effect of berberine neither occurred in intracellular targets nor extracellular cholecystokinin (CCK) receptors, chloride (Cl-) channels, and store-operated Ca2+ channels. Together, the results demonstrate that berberine directly inhibits the muscarinic M3 receptors, further confirmed by evidence of the interaction between berberine and M3 receptors in pancreatic acinar cells.


Subject(s)
Acinar Cells , Berberine , Calcium Signaling , Receptor, Muscarinic M3 , Animals , Berberine/pharmacology , Receptor, Muscarinic M3/metabolism , Receptor, Muscarinic M3/antagonists & inhibitors , Mice , Acinar Cells/drug effects , Acinar Cells/metabolism , Calcium Signaling/drug effects , Calcium Signaling/physiology , Pancreas/drug effects , Pancreas/metabolism , Male , Acetylcholine/metabolism , Calcium/metabolism , Dose-Response Relationship, Drug
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