title: Cannabinoid receptors CB1 and CB2 form functional heteromers in brain.
abstract: Exploring the role of cannabinoid CB(2) receptors in the brain, we present evidence of CB(2) receptor molecular and functional interaction with cannabinoid CB(1) receptors. Using biophysical and biochemical approaches, we discovered that CB(2) receptors can form heteromers with CB(1) receptors in transfected neuronal cells and in rat brain pineal gland, nucleus accumbens, and globus pallidus. Within CB(1)-CB(2) receptor heteromers expressed in a neuronal cell model, agonist co-activation of CB(1) and CB(2) receptors resulted in a negative cross-talk in Akt phosphorylation and neurite outgrowth. Moreover, one specific characteristic of CB(1)-CB(2) receptor heteromers consists of both the ability of CB(1) receptor antagonists to block the effect of CB(2) receptor agonists and, conversely, the ability of CB(2) receptor antagonists to block the effect of CB(1) receptor agonists, showing a bidirectional cross-antagonism phenomenon. Taken together, these data illuminate the mechanism by which CB(2) receptors can negatively modulate CB(1) receptor function.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Callén
authors.forename: Estefanía
authors.initials: E
authors.lastname: Moreno
authors.forename: Pedro
authors.initials: P
authors.lastname: Barroso-Chinea
authors.forename: David
authors.initials: D
authors.lastname: Moreno-Delgado
authors.forename: Antoni
authors.initials: A
authors.lastname: Cortés
authors.forename: Josefa
authors.initials: J
authors.lastname: Mallol
authors.forename: Vicent
authors.initials: V
authors.lastname: Casadó
authors.forename: José Luis
authors.initials: JL
authors.lastname: Lanciego
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Carmen
authors.initials: C
authors.lastname: Lluis
authors.forename: Enric I
authors.initials: EI
authors.lastname: Canela
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCormick
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005917:Globus Pallidus / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D010870:Pineal Gland / Q000378:metabolism*; D055503:Protein Multimerization / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C469526:Cnr2 protein, rat; D009419:Nerve Tissue Proteins; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D051057:Proto-Oncogene Proteins c-akt