BACKGROUND AND PURPOSE:

Although cannabinoid CB₂ receptor ligands have been widely characterized in recombinant systems in vitro, little pharmacological characterization has been performed in tissues natively expressing CB₂ receptors. The aim of this study was to compare the pharmacology of CB₂ receptor ligands in tissue natively expressing CB₂ receptors (human, rat and mouse spleen) and hCB₂ -transfected CHO cells.

EXPERIMENTAL APPROACH:

We tested the ability of well-known cannabinoid CB₂ receptor ligands to stimulate or inhibit [³⁵S]GTPγS binding to mouse, rat and human spleen membranes and to hCB₂ -transfected CHO cell membranes. cAMP assays were also performed in hCB₂ -CHO cells.

KEY RESULTS:

The data presented demonstrate that: (i) CP 55,940, WIN 55,212-2 and JWH 133 behave as CB₂ receptor full agonists both in spleen and hCB₂ -CHO cells, in both [³⁵ S]GTPγS and cAMP assays; (ii) JWH 015 behaves as a low-efficacy agonist in spleen as well as in hCB₂ -CHO cells when tested in the [³⁵ S]GTPγS assay, while it displays full agonism when tested in the cAMP assay using hCB₂ -CHO cells; (iii) (R)-AM 1241 and GW 405833 behave as agonists in the [³⁵ S]GTPγS assay using spleen, instead it behaves as a low-efficacy inverse agonist in hCB₂ -CHO cells; and (iv) SR 144528, AM 630 and JTE 907 behave as CB₂ receptor inverse agonists in all the tissues.

CONCLUSION AND IMPLICATIONS:

Our results demonstrate that CB₂ receptor ligands can display differential pharmacology when assays are conducted in tissues that natively express CB₂ receptors and imply that conclusions from recombinant CB₂receptors should be treated with caution.
© 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

PMID:

 

23711022

 

[PubMed – as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23711022