title: Endocannabinoid transport revisited.
abstract: Endocannabinoids are arachidonic acid-derived endogenous lipids that activate the endocannabinoid system which plays a major role in health and disease. The primary endocannabinoids are anandamide (AEA, N-arachidonoylethanolamine) and 2-arachidonoyl glycerol. While their biosynthesis and metabolism have been studied in detail, it remains unclear how endocannabinoids are transported across the cell membrane. In this review, we critically discuss the different models of endocannabinoid trafficking, focusing on AEA cellular uptake which is best studied. The evolution of the current knowledge obtained with different AEA transport inhibitors is reviewed and the confusions caused by the lack of their specificity discussed. A comparative summary of the most important AEA uptake inhibitors and the studies involving their use is provided. Based on a comprehensive literature analysis, we propose a model of facilitated AEA membrane transport followed by intracellular shuttling and sequestration. We conclude that novel and more specific probes will be essential to identify the missing targets involved in endocannabinoid membrane transport.
authors.affiliation: Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, Bern, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Nicolussi
authors.affiliation: Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, Bern, Switzerland. Electronic address: gertsch@ibmm.unibe.ch.
authors.forename: Jürg
authors.initials: J
authors.lastname: Gertsch
mesh_terms: D000818:Animals; D001095:Arachidonic Acids; D001692:Biological Transport / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D006801:Humans; D053284:Polyunsaturated Alkamides
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide
keywords: 2-AG; Anandamide; Endocannabinoid system; Endocannabinoid uptake and transport; Endocannabinoid uptake inhibitor; FAAH; Membrane transporter