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(Hypertension. 2008;52:601.)
© 2008 American Heart Association, Inc.

Brief Reviews

Modulation of the Endocannabinoid System in Cardiovascular Disease

Therapeutic Potential and Limitations

Pál Pacher; Partha Mukhopadhyay; Rajesh Mohanraj; Grzegorz Godlewski; Sándor Bátkai; George Kunos

From the Sections on Oxidative Stress Tissue Injury (P.P., P.M., R.M.) and Neuroendocrinology (G.G., S.B., G.K.), Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Md.

Correspondence to Pál Pacher, National Institute on Alcohol Abuse and Alcoholism, 5625 Fishers Lane, MSC-9413, Bethesda, MD 20892-9413. E-mail pacher@mail.nih.gov

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Endocannabinoids, endogenous lipid mediators generated by virtually all cell types both in the brain and peripheral tissues, elicit a broad range of biological effects similar to those of marijuana. The endocannabinoid system (ECS) comprises the endocannabinoids, the enzymes involved in their biosynthesis and degradation, putative membrane transporter(s) involved in their cellular uptake and (possibly) release, and the G protein-coupled receptors that mediate their effects, including CB₁ and CB₂ as well as additional, as yet unidentified, receptors.^1–4 GPR55 has recently been proposed to be a cannabinoid receptor,⁵ although its in vivo biological functions have not yet been identified. Arachidonoyl ethanolamide (anandamide [AEA]) and 2-arachidonoylglycerol are the 2 best characterized endocannabinoids. AEA can be a full or partial agonist at CB₁ receptors, depending on the system, and has low efficacy at CB₂ receptors, whereas 2-arachidonoylglycerol is a full agonist at both CB₁ and CB₂ receptors. AEA also binds to vanilloid VR₁ receptors, although with an affinity an order of magnitude lower than its affinity for CB₁ receptors.³ Both AEA and 2-arachidonoylglycerol are generated in the cell membrane from membrane phospholipid precursors, and the synthesis of both ligands involves multiple, parallel biosynthetic pathways.^4,6,7 In contrast, their enzymatic degradation occurs through unique pathways, AEA being degraded primarily by fatty acid amidohydrolase (FAAH),⁸ whereas 2-arachidonoylglycerol is degraded mainly by monoglyceride lipase, although additional enzymes may make a minor contribution to the in vivo degradation of both ligands.⁹ In the absence of a cellular storage mechanism for endocannabinoids, their tissue levels are determined by the balance . . . [Full Text of this Article]

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