title: Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca(2+) oscillations in mouse pancreatic acinar cells.
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 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R 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, 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 CB2Rs 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 CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-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 CB2Rs 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 CB2R-mediated protection in acute pancreatitis.
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital, Central South University, and Key Laboratory of Viral Hepatitis, Hunan Province, Changsha 410008, China.|Departments of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix AZ 85013, USA.
authors.forename: Zebing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Jingke
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Mengqin
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Shen
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Departments of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix AZ 85013, USA.
authors.forename: Kunkun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Departments of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix AZ 85013, USA.
authors.forename: Dejie
authors.initials: D
authors.lastname: Chen
authors.affiliation: Departments of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix AZ 85013, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ 85004, USA.|Departments of Pharmacology and Psychiatry University of Arizona College of Medicine Tucson, AZ, 85721, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Hammer
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Zhengxiong
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital, Central South University, and Key Laboratory of Viral Hepatitis, Hunan Province, Changsha 410008, China.
authors.forename: Xuegong
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital, Central South University, and Key Laboratory of Viral Hepatitis, Hunan Province, Changsha 410008, China.|Departments of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix AZ 85013, USA.|Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China.|Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ 85004, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D061354:Acinar Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D018679:Cholinergic Agonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology*; D010179:Pancreas / Q000166:cytology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
chemical_list: C463040:1-(2,3-dichlorobenzoyl)-5-methoxy-2-methyl-(2-(mopholin-4-yl)ethyl)-1H-indole; D018679:Cholinergic Agonists; D007211:Indoles; D009025:Morpholines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D001120:Arginine; D000109:Acetylcholine; D002118:Calcium