Heterogeneity of cannabinoid ligand-induced modulations in intracellular Ca 2+ signals of mouse pancreatic acinar cells in vitro

Kun kun Xia, Jian xin Shen, Ze bing Huang, Hui min Song, Ming Gao, De jie Chen, Shui jun Zhang, Jie Wu

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

We recently reported that a CB 2 R agonist, GW405833 (GW), reduced both the ACh-induced Ca 2+ oscillations and the L-arginine-induced Ca 2+ signal enhancement in mouse pancreatic acinar cells, suggesting that GW-induced inhibition may prevent the pathogenesis of acute pancreatitis. In this study, we aim to evaluate the effects of other cannabinoid ligands on Ca 2+ signaling in acinar cells. Patch-clamp whole-cell recordings were applied to measure ACh-induced intracellular Ca 2+ oscillations in pancreatic acinar cells acutely dissociated from wild-type (WT), CB 1 R knockout (KO), and CB 2 R KO mice, and the pharmacological effects of various cannabinoid ligands on the Ca 2+ oscillations were examined. We found that all the 8 CB 2 R agonists tested inhibited ACh-induced Ca 2+ oscillations. Among them, GW, JWH133, and GP1a caused potent inhibition with IC 50 values of 5.0, 6.7, and 1.2 μmol/L, respectively. In CB 2 R KO mice or in the presence of a CB 2 R antagonist (AM630), the inhibitory effects of these 3 CB 2 R agonists were abolished, suggesting that they acted through the CB 2 Rs. The CB 1 R agonist ACEA also induced inhibition of Ca 2+ oscillations that existed in CB 1 R KO mice and in the presence of a CB 1 R antagonist (AM251), suggesting a non-CB 1 R effect. In WT, CB 1 R KO, and CB 2 R KO mice, a nonselective CBR agonist, WIN55,212-2, inhibited Ca 2+ oscillations, which was not mediated by CB 1 Rs or CB 2 Rs. The endogenous cannabinoid substance, 2-arachidonoylglycerol (2-AG), did not show an inhibitory effect on Ca 2+ oscillations. In conclusion, CB 2 R agonists play critical roles in modulating Ca 2+ signals in mouse pancreatic acinar cells, while other cannabinoid ligands modulate Ca 2+ oscillations in a heterogeneous manner through a CB receptor or non-CB-receptor mechanism.

Original languageEnglish (US)
Pages (from-to)410-417
Number of pages8
JournalActa Pharmacologica Sinica
Volume40
Issue number3
DOIs
StatePublished - Mar 1 2019
Externally publishedYes

Keywords

  • cannabinoid
  • CB receptor
  • CB receptor
  • endocannabinoid; Ca oscillations; pancreatic acinar cells
  • patch-clamp

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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