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Endocannabinoids and cannabinoid receptors in ischaemia–reperfusion injury and preconditioning
Author(s) -
Pacher P,
Haskó G
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707582
Subject(s) - cannabinoid receptor , endocannabinoid system , cannabinoid , reperfusion injury , cannabinoid receptor type 2 , receptor , pharmacology , medicine , ischemia , agonist
Ischaemia–reperfusion (I/R) is a pivotal mechanism of organ injury during stroke, myocardial infarction, organ transplantation and vascular surgeries. Ischaemic preconditioning (IPC) is a potent endogenous form of tissue protection against I/R injury. On the one hand, endocannabinoids have been implicated in the protective effects of IPC through cannabinoid CB 1 /CB 2 receptor‐dependent and ‐independent mechanisms. However, there is evidence suggesting that endocannabinoids are overproduced during various forms of I/R, such as myocardial infarction or whole body I/R associated with circulatory shock, and may contribute to the cardiovascular depressive state associated with these pathologies. Previous studies using synthetic CB 1 receptor agonists or knockout mice demonstrated CB 1 receptor‐dependent protection against cerebral I/R injury in various animal models. In contrast, several follow‐up reports have shown protection afforded by CB 1 receptor antagonists, but not agonists. Excitedly, emerging studies using potent CB 2 receptor agonists and/or knockout mice have provided compelling evidence that CB 2 receptor activation is protective against myocardial, cerebral and hepatic I/R injuries by decreasing the endothelial cell activation/inflammatory response (for example, expression of adhesion molecules, secretion of chemokines, and so on), and by attenuating the leukocyte chemotaxis, rolling, adhesion to endothelium, activation and transendothelial migration, and interrelated oxidative/nitrosative damage. This review is aimed to discuss the role of endocannabinoids and CB receptors in various forms of I/R injury (myocardial, cerebral, hepatic and circulatory shock) and preconditioning, and to delineate the evidence supporting the therapeutic utility of selective CB 2 receptor agonists, which are devoid of psychoactive effects, as a promising new approach to limit I/R‐induced tissue damage. British Journal of Pharmacology (2008) 153 , 252–262; doi: 10.1038/sj.bjp.0707582 ; published online 19 November 2007