title: Human brain endothelium: coexpression and function of vanilloid and endocannabinoid receptors.
abstract: The arachidonic acid derivative, 2-arachidonoyl-glycerol (2-AG), was initially isolated from gut and brain; it is also produced and released from blood and vascular cells. Many of the 2-AG-induced cellular responses (i.e., neuromodulation, cytoprotection and vasodilation) are mediated by cannabinoid receptors CB1 and CB2. The findings presented here demonstrate the expression of CB1, CB2 and TRPV1 receptors on cerebromicrovascular endothelial cells (HBEC). The expression of TRPV1, CB1 and CB2 receptor mRNA and proteins were demonstrated by RT-PCR and polyclonal antibodies, respectively. The endocannabinoid 2-AG, and other related compounds [anandamide (ANA), methanandamide (m-ANA), N-(4-hydroxyphenyl-arachidonyl-ethanolamide) (AM404) and capsaicin] dose-dependently stimulated Ca2+ influx in HBEC. The selective TRPV1 receptor antagonist (capsazepine), CB1 receptor antagonist (SR141716A) and CB2 receptor antagonist (SR144528) inhibited these responses. The effects of capsaicin, a specific agonist for TRPV1 receptors, were inhibited by capsazepine, but only weakly by CB1 or CB2 receptor antagonists. 2-AG also induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP); this response was mediated by VR1 receptors. These studies clearly indicate that 2-AG and other related compounds may function as agonists on VR1 receptors, as well as CB1 and CB2 receptors, and implicated these factors in various HBEC functions.
authors.affiliation: Resuscitative Medicine Department, Naval Medical Research Center, Bethesda, MD, USA.
authors.forename: Susanne Andrea
authors.initials: SA
authors.lastname: Golech
authors.forename: Richard M
authors.initials: RM
authors.lastname: McCarron
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Joliet
authors.initials: J
authors.lastname: Bembry
authors.forename: Frederick
authors.initials: F
authors.lastname: Lenz
authors.forename: Raphael
authors.initials: R
authors.lastname: Mechoulam
authors.forename: Esther
authors.initials: E
authors.lastname: Shohami
authors.forename: Maria
authors.initials: M
authors.lastname: Spatz
mesh_terms: D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D001892:Camphanes / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism* / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D063388:Endocannabinoids; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism*; D008840:Microfilament Proteins; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism*; D011955:Receptors, Drug / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D050916:TRPV Cation Channels; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D001095:Arachidonic Acids; D001892:Camphanes; D063386:Cannabinoid Receptor Agonists; D063385:Cannabinoid Receptor Modulators; D015815:Cell Adhesion Molecules; D063388:Endocannabinoids; D005989:Glycerides; D007473:Ion Channels; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C110630:SR 144528; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D000098662:Vasodilator-Stimulated Phosphoprotein; C094503:glyceryl 2-arachidonate; C071423:capsazepine; D000077285:Rimonabant; D002211:Capsaicin; C078814:anandamide