Background and purpose
Although cannabinoid CB&sub2; receptor ligands have been widely characterized in recombinant systems in vitro, little pharmacological characterization has been performed in tissues natively expressing CB&sub2; receptors. The aim of this study was to compare the pharmacology of CB&sub2; receptor ligands in tissue natively expressing CB&sub2; receptors (human, rat and mouse spleen) and hCB&sub2;-transfected CHO cells. Experimental approach: We tested the ability of well-known cannabinoid CB&sub2; receptor ligands to stimulate or inhibit [³&sup5;S]GTPγS binding to mouse, rat and human spleen membranes and to hCB&sub2;-transfected CHO cell membranes. cAMP assays were also performed in hCB&sub2;-CHO cells. Key
Purpose
Although cannabinoid CB&sub2; receptor ligands have been widely characterized in recombinant systems in vitro, little pharmacological characterization has been performed in tissues natively expressing CB&sub2; receptors. The aim of this study was to compare the pharmacology of CB&sub2; receptor ligands in tissue natively expressing CB&sub2; receptors (human, rat and mouse spleen) and hCB&sub2;-transfected CHO cells. Experimental approach: We tested the ability of well-known cannabinoid CB&sub2; receptor ligands to stimulate or inhibit [³&sup5;S]GTPγS binding to mouse, rat and human spleen membranes and to hCB&sub2;-transfected CHO cell membranes. cAMP assays were also performed in hCB&sub2;-CHO cells. Key
Results
The data presented demonstrate that: (i) CP 55,940, WIN 55,212-2 and JWH 133 behave as CB&sub2; receptor full agonists both in spleen and hCB&sub2;-CHO cells, in both [³&sup5;S]GTPγS and cAMP assays; (ii) JWH 015 behaves as a low-efficacy agonist in spleen as well as in hCB&sub2;-CHO cells when tested in the [³&sup5;S]GTPγS assay, while it displays full agonism when tested in the cAMP assay using hCB&sub2;-CHO cells; (iii) (R)-AM 1241 and GW 405833 behave as agonists in the [³&sup5;S]GTPγS assay using spleen, instead it behaves as a low-efficacy inverse agonist in hCB&sub2;-CHO cells; and (iv) SR 144528, AM 630 and JTE 907 behave as CB&sub2; receptor inverse agonists in all the tissues.