Cannabinoid receptors CB1 and CB2 form functional heteromers in brain

Callén, Lucía, Moreno, Estefanía, Barroso-Chinea, Pedro, Moreno-Delgado, David, Cortés, Antoni, Mallol, Josefa, Casadó, Vicent, Lanciego, José Luis, Franco, Rafael, Lluis, Carmen, Canela, Enric I and McCormick, Peter J (2012) Cannabinoid receptors CB1 and CB2 form functional heteromers in brain. The Journal of Biological Chemistry, 287 (25). pp. 20851-65. ISSN 1083-351X

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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.

Item Type: Article
Uncontrolled Keywords: animals,cell line, tumor,globus pallidus,hek293 cells,humans,male,nerve tissue proteins,nucleus accumbens,phosphorylation,pineal gland,protein multimerization,proto-oncogene proteins c-akt,rats,rats, sprague-dawley,receptor, cannabinoid, cb1,receptor, cannabinoid, cb2
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 13 Jan 2014 13:10
Last Modified: 24 Oct 2022 05:56
DOI: 10.1074/jbc.M111.335273

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