2014 Jun 23. pii: S0014-4886(14)00204-0. doi: 10.1016/j.expneurol.2014.06.017. [Epub ahead of print]
CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum.
Martínez-Pinilla E1, Reyes-Resina I2, Oñatibia-Astibia A3, Zamarbide M3, Ricobaraza A4, Navarro G2, Moreno E2, Dopeso-Reyes IG5, Sierra S5, Rico AJ5, Roda E5, Lanciego JL5, Franco R6.
Abstract
Heteromerization of G-protein-coupled receptors is an important event as they integrate the actions of extracellular signals to give heteromer-selective ligand binding and signaling, opening new avenues in the development of potential drug targets in pharmacotherapy. A further aim of the present paper was to check for cannabinoid CB1-GPR55 receptor heteromers in the central nervous system (CNS), specifically in striatum. First, a direct interaction was demonstrated in cells transfected with the cDNA for the human version of the receptors, using bioluminescence resonance energy transfer and in situ proximity ligation assays (PLA). In the heterologous system, a biochemical fingerprint consisting on cross-antagonism in ERK1/2 phosphorylation was detected. The cross-antagonism was also observed on GPR55-mediated NFAT activation. Direct identification of GPR55 receptors in striatum is here demonstrated in rat brain slices using a specific agonist. Moreover, the heteromer fingerprint was identified in these rat slices by ERK1/2 phosphorylation assays whereas PLA assays showed results consistent with receptor-receptor interaction in both caudate and putamen nucleus of a non-human primate. The results indicate not only that GPR55 is expressed in striatum but CB1 and GPR55 receptors form heteromers in this specific CNS region.
Copyright © 2014. Published by Elsevier Inc.
Copyright © 2014. Published by Elsevier Inc.
KEYWORDS:
BRET; Cannabinoids; GPCR heteromerization; PLA
- PMID:
- 24967683
- [PubMed – as supplied by publisher]
