Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

Zebing Huang, Haiyan Wang, Jingke Wang, Mengqin Zhao, Nana Sun, Fangfang Sun, Jianxin Shen, Haiying Zhang, Kunkun Xia, Dejie Chen, Ming Gao, Ronald P. Hammer, Qingrong Liu, Zhengxiong Xi, Xuegong Fan, Jie Wu

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Emerging evidence demonstrates that the blockade of intracellular Ca 2+ signals may protect pancreatic acinar cells against Ca 2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB 2 R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB 2 Rs modulate intracellular Ca 2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB 2 R agonist, GW405833 (GW) in agonist-induced Ca 2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB 1 R-knockout (KO), and CB 2 R-KO mice. Immunohistochemical labeling revealed that CB 2 R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB 2 Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca 2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB 2 R antagonist, AM630, or was absent in CB 2 R-KO but not CB 1 R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca 2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB 2 Rs eliminates ACh-induced Ca 2+ oscillations and L-arginine-induced enhancement of Ca 2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB 2 R-mediated protection in acute pancreatitis.

Original languageEnglish (US)
Article number29757
JournalScientific reports
Volume6
DOIs
StatePublished - Jul 19 2016

ASJC Scopus subject areas

  • General

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