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

Persistent Link:
http://hdl.handle.net/10150/618957
Title:
Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells
Author:
Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P.; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie
Affiliation:
Univ Arizona, Dept Basic Med Sci, Coll Med; Univ Arizona, Coll Med, Dept Pharmacol; Univ Arizona, Coll Med, Dept Psychiat
Issue Date:
2016-07-19
Publisher:
NATURE PUBLISHING GROUP
Citation:
Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells 2016, 6:29757 Scientific Reports
Journal:
Scientific Reports
Rights:
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract:
Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB(2)Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R 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 Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB(2)Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis.
Note:
Open Access Journal
ISSN:
2045-2322
PubMed ID:
27432473
DOI:
10.1038/srep29757
Version:
Final published version
Sponsors:
Seed Fund of Shangtou University Medical College; Guangdong Science and Technology Foundation
Additional Links:
http://www.nature.com/articles/srep29757

Full metadata record

DC FieldValue Language
dc.contributor.authorHuang, Zebingen
dc.contributor.authorWang, Haiyanen
dc.contributor.authorWang, Jingkeen
dc.contributor.authorZhao, Mengqinen
dc.contributor.authorSun, Nanaen
dc.contributor.authorSun, Fangfangen
dc.contributor.authorShen, Jianxinen
dc.contributor.authorZhang, Haiyingen
dc.contributor.authorXia, Kunkunen
dc.contributor.authorChen, Dejieen
dc.contributor.authorGao, Mingen
dc.contributor.authorHammer, Ronald P.en
dc.contributor.authorLiu, Qingrongen
dc.contributor.authorXi, Zhengxiongen
dc.contributor.authorFan, Xuegongen
dc.contributor.authorWu, Jieen
dc.date.accessioned2016-08-27T00:49:41Z-
dc.date.available2016-08-27T00:49:41Z-
dc.date.issued2016-07-19-
dc.identifier.citationCannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells 2016, 6:29757 Scientific Reportsen
dc.identifier.issn2045-2322-
dc.identifier.pmid27432473-
dc.identifier.doi10.1038/srep29757-
dc.identifier.urihttp://hdl.handle.net/10150/618957-
dc.description.abstractEmerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB(2)Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R 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 Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB(2)Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis.en
dc.description.sponsorshipSeed Fund of Shangtou University Medical College; Guangdong Science and Technology Foundationen
dc.language.isoenen
dc.publisherNATURE PUBLISHING GROUPen
dc.relation.urlhttp://www.nature.com/articles/srep29757en
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.titleCannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cellsen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Basic Med Sci, Coll Meden
dc.contributor.departmentUniv Arizona, Coll Med, Dept Pharmacolen
dc.contributor.departmentUniv Arizona, Coll Med, Dept Psychiaten
dc.identifier.journalScientific Reportsen
dc.description.noteOpen Access Journalen
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen

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