Cannabinoid Receptor Subtype 2 (Cb2R) Agonist Gw405833 Reduces Agonist-Induced Ca2+ Oscillations In Mouse Pancreatic Acinar Cells

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

Spatial inhomogeneity of point defect properties in refractory multi principal element alloy with short range order: A first principles study

Short range order can be developed in multi principal element alloys and influences the point defect behavior due to the large variation of the local chemical environment. The effect of short range order on vacancy and interstitial formation energy and migration behavior was studied in body centered cubic multi principal element alloy NbZrTi by first principles calculations. Two short range order structures created by density functional theory and Monte Carlo method at 500 and 800 K were compared with the structure of random solid solution. Both vacancy and interstitial formation energies increase with the degree of short range order. Point defect formation energies tend to be higher in regions enriched in Nb and lower in regions enriched in Zr and Ti. Both vacancies and interstitials prefer to migrate toward Zr,Ti rich regions and away from Nb rich regions, suggesting that Zr,Ti rich regions can potentially act as recombination centers for point defect annihilation. Compared to an ideal random solid solution, the short range order increases the spatial inhomogeneity of point defect energy landscape. Tuning the degree of short range order by different processing techniques can be a viable strategy to optimize the point defect behavior to achieve enhanced radiation resistance in multi principal element alloys

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

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.Seed Fund of Shangtou University Medical College; Guangdong Science and Technology FoundationOpen Access JournalThis 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 [email protected]