Human brain endothelium: coexpression and function of vanilloid and endocannabinoid receptors

• Published in: Brain research. Molecular brain research. Vol. 132; no. 1; pp. 87 - 92
• Main Authors: Golech, Susanne Andrea, McCarron, Richard M., Chen, Ye, Bembry, Joliet, Lenz, Frederick, Mechoulam, Raphael, Shohami, Esther, Spatz, Maria
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 06.12.2004; Elsevier
• Subjects: Arachidonic Acids - metabolism; Arachidonic Acids - pharmacology; Biological and medical sciences; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiology; Bornanes - pharmacology; Brain - blood supply; Brain - metabolism; Brain endothelium; Ca 2+influx; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators - metabolism; Cannabinoid Receptor Modulators - pharmacology; Capsaicin - analogs & derivatives; Capsaicin - metabolism; Capsaicin - pharmacology; Cell Adhesion Molecules - drug effects; Cell Adhesion Molecules - metabolism; Cells, Cultured; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; Dose-Response Relationship, Drug; Drug Interactions - physiology; Endocannabinoids; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Fundamental and applied biological sciences. Psychology; Glycerides - metabolism; Glycerides - pharmacology; Humans; Ion Channels - agonists; Ion Channels - genetics; Ion Channels - metabolism; Microcirculation - drug effects; Microcirculation - metabolism; Microfilament Proteins; Phosphoproteins - drug effects; Phosphoproteins - metabolism; Phosphorylation - drug effects; Piperidines - pharmacology; Polyunsaturated Alkamides; Pyrazoles - pharmacology; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - metabolism; Receptor, Cannabinoid, CB2 - agonists; Receptor, Cannabinoid, CB2 - genetics; Receptor, Cannabinoid, CB2 - metabolism; Receptors; Receptors, Cannabinoid - genetics; Receptors, Cannabinoid - metabolism; Receptors, Drug - agonists; Receptors, Drug - genetics; Receptors, Drug - metabolism; RNA, Messenger - drug effects; RNA, Messenger - metabolism; TRPV Cation Channels; VASP; Vertebrates: nervous system and sense organs; VASP; Brain endothelium; Cellular and molecular biology; Receptors; Endocannabinoids; Ca 2+influx; Human; Central nervous system; Vanilloid receptor; Cannabinoid; Ca2+influx; Encephalon; Endothelium; Biological receptor
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/j.molbrainres.2004.08.025

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 CB 1 and CB 2. The findings presented here demonstrate the expression of CB 1, CB 2 and TRPV1 receptors on cerebromicrovascular endothelial cells (HBEC). The expression of TRPV1, CB 1 and CB 2 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 Ca 2+ influx in HBEC. The selective TRPV1 receptor antagonist (capsazepine), CB 1 receptor antagonist (SR141716A) and CB 2 receptor antagonist (SR144528) inhibited these responses. The effects of capsaicin, a specific agonist for TRPV1 receptors, were inhibited by capsazepine, but only weakly by CB 1 or CB 2 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 CB 1 and CB 2 receptors, and implicated these factors in various HBEC functions.