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Allosteric Modulation of Cannabinoid CB 1 Receptor
Author(s) -
Ross Ruth A.,
Baillie Gemma L.,
Pertwee Roger G.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.836.6
Subject(s) - allosteric regulation , chemistry , allosteric modulator , agonist , cannabinoid receptor agonists , cannabinoid , pharmacology , cannabinoid receptor , receptor , cannabinoid receptor type 2 , biochemistry , biology
ORG27569, an allosteric modulator of the cannabinoid CB 1 receptor increases the binding affinity of CB 1 receptor agonists but reduces the agonist signalling efficacy. Allosteric modulators can have differential effects on various signalling pathways. The aim of the present study was to investigate the effect of ORG27569 on various agonist‐induced CB 1 receptor signalling pathways. ORG27569 (100 nM) markedly reduced the efficacy of CP55940 in the [ 35 S]GTPγS binding assay, β arrestin assay and cyclic AMP assay. In contrast, 1μM ORG2759 had no significant effect on the efficacy of CP55940 in pERK assay. These data provide evidence that cannabinoid CB 1 receptor allosteric modulators can preferentially impact various signalling pathways.