Berberine inhibits intracellular Ca2+ signals in mouse pancreatic acinar cells through M3 muscarinic receptors: Novel target, mechanism, and implication

Kunkun Xia; Zhijun Hei; Shuangtao Li; Huimin Song; Rongni Huang; Xiaoyu Ji; Fenni Zhang; Jianxin Shen; Shuijun Zhang; Shuang Peng; Jie Wu

doi:10.1016/j.bcp.2024.116279

Berberine inhibits intracellular Ca²⁺ signals in mouse pancreatic acinar cells through M₃ muscarinic receptors: Novel target, mechanism, and implication

Biochem Pharmacol. 2024 May 11:225:116279. doi: 10.1016/j.bcp.2024.116279. Online ahead of print.

Authors

Kunkun Xia¹, Zhijun Hei¹, Shuangtao Li², Huimin Song², Rongni Huang², Xiaoyu Ji³, Fenni Zhang⁴, Jianxin Shen², Shuijun Zhang⁵, Shuang Peng⁶, Jie Wu⁷

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Department of Colorectal Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
² Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong 515041, China.
³ Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China.
⁴ Center for Bioelectronics and Biosensors, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
⁵ Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
⁶ School of Sport and Health Sciences, Guangzhou Sport University, Guangzhou 510000, China.
⁷ Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Neurobiology, Barrow Neurological Institute, Phoenix 85013, USA.

PMID: 38740221
DOI: 10.1016/j.bcp.2024.116279

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.

Keywords: Brberine; Ca(2+) oscillation; Intracellular Ca(2+)signal; M(3) muscarinic receptor; Pancreatic acinar cell; Patch-clamp.