Endocannabinoids and cannabinoid receptors in ischaemia-reperfusion injury and preconditioning

P. Pacher, G. Haskó

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)252-262
Number of pages11
JournalBritish Journal of Pharmacology
Volume153
Issue number2
DOIs
Publication statusPublished - Jan 2008

Fingerprint

Cannabinoid Receptors
Endocannabinoids
Reperfusion Injury
Reperfusion
Ischemia
Ischemic Preconditioning
Brain Ischemia
Knockout Mice
Shock
Myocardial Infarction
Leukocyte Chemotaxis
Leukocyte Rolling
Transendothelial and Transepithelial Migration
Cannabinoids
Liver
Organ Transplantation
Chemokines
Endothelium
Blood Vessels
Endothelial Cells

Keywords

  • Cannabinoid receptors
  • Endocannabinoids
  • Inflammation
  • Ischaemia-reperfusion
  • Leukocyte chemotaxis and adhesion
  • Preconditioning

ASJC Scopus subject areas

  • Pharmacology

Cite this

Endocannabinoids and cannabinoid receptors in ischaemia-reperfusion injury and preconditioning. / Pacher, P.; Haskó, G.

In: British Journal of Pharmacology, Vol. 153, No. 2, 01.2008, p. 252-262.

Research output: Contribution to journalArticle

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