title: Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids.
abstract: The mechanism of action responsible for the motor depressant effects of cannabinoids, which operate through centrally expressed cannabinoid CB1 receptors, is still a matter of debate. In the present study, we report that CB1 and adenosine A2A receptors form heteromeric complexes in co-transfected HEK-293T cells and rat striatum, where they colocalize in fibrilar structures. In a human neuroblastoma cell line, CB1 receptor signaling was found to be completely dependent on A2A receptor activation. Accordingly, blockade of A2A receptors counteracted the motor depressant effects produced by the intrastriatal administration of a cannabinoid CB1 receptor agonist. These biochemical and behavioral findings demonstrate that the profound motor effects of cannabinoids depend on physical and functional interactions between striatal A2A and CB1 receptors.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Paulina
authors.initials: P
authors.lastname: Carriba
authors.forename: Oskar
authors.initials: O
authors.lastname: Ortiz
authors.forename: Kshitij
authors.initials: K
authors.lastname: Patkar
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Justinova
authors.forename: Jessica
authors.initials: J
authors.lastname: Stroik
authors.forename: Andrea
authors.initials: A
authors.lastname: Themann
authors.forename: Christa
authors.initials: C
authors.lastname: Müller
authors.forename: Anima S
authors.initials: AS
authors.lastname: Woods
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Hope
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.forename: Vicent
authors.initials: V
authors.lastname: Casadó
authors.forename: Enric I
authors.initials: EI
authors.lastname: Canela
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
authors.forename: Rosario
authors.initials: R
authors.lastname: Moratalla
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001522:Behavior, Animal; D002186:Cannabinoids / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002461:Cell Line, Transformed; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000172:deficiency / Q000502:physiology*; D014162:Transfection
chemical_list: D058908:Adenosine A2 Receptor Agonists; D001095:Arachidonic Acids; D002186:Cannabinoids; D008164:Luminescent Proteins; D043705:Receptor, Adenosine A2A; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; D000242:Cyclic AMP