Endocannabinoids and their involvement in the neurovascular system.
Endocannabinoids are a new class of lipids, which include amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of Delta(9)-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana. It is known that the activity of AEA is limited by cellular uptake through a specific membrane transporter, followed by intracellular degradation by a fatty acid amide hydrolase. Together with AEA and congeners these proteins form the "endocannabinoid system". The endogenous cannabinoids were identified in brain, and also in neuronal and endothelial cells, suggesting a potential role as modulators in the central nervous system and in the periphery. This review summarises the metabolic routes for the synthesis and degradation of AEA, and the latest advances in the involvement of this lipid in neurovascular biology. In addition, the therapeutic potential of the modulation of endocannabinoid metabolism for neuronal and vascular system will be also reviewed.
Battista
Natalia
N
Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, I-64100 Teramo, Italy.
Fezza
Filomena
F
Maccarrone
Mauro
M
D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000378:metabolism; D001808:Blood Vessels / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002319:Cardiovascular System / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D063388:Endocannabinoids; D006801:Humans; D009103:Multiple Sclerosis / Q000378:metabolism; D009420:Nervous System / Q000098:blood supply*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D053284:Polyunsaturated Alkamides
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide