Fiona Templeton

University of Aberdeen, Aberdeen, SCT, United Kingdom

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Publications (1)5.07 Total impact

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    ABSTRACT: We have tested our prediction that AM630 is a CB2 cannabinoid receptor ligand and also investigated whether L759633 and L759656, are CB2 receptor agonists.Binding assays with membranes from CHO cells stably transfected with human CB1 or CB2 receptors using [3H]-CP55940, confirmed the CB2-selectivity of L759633 and L759656 (CB2/CB1 affinity ratios=163 and 414 respectively) and showed AM630 to have a Ki at CB2 receptors of 31.2 nM and a CB2/CB1 affinity ratio of 165.In CB2-transfected cells, L759633 and L759656 were potent inhibitors of forskolin-stimulated cyclic AMP production, with EC50 values of 8.1 and 3.1 nM respectively and CB1/CB2 EC50 ratios of >1000 and >3000 respectively.AM630 inhibited [35S]-GTPγS binding to CB2 receptor membranes (EC50=76.6 nM), enhanced forskolin-stimulated cyclic AMP production in CB2-transfected cells (5.2 fold by 1 μM), and antagonized the inhibition of forskolin-stimulated cyclic AMP production in this cell line induced by CP55940.In CB1-transfected cells, forskolin-stimulated cyclic AMP production was significantly inhibited by AM630 (22.6% at 1 μM and 45.9% at 10 μM) and by L759633 at 10 μM (48%) but not 1 μM. L759656 (10 μM) was not inhibitory. AM630 also produced a slight decrease in the mean inhibitory effect of CP55940 on cyclic AMP production which was not statistically significant.We conclude that AM630 is a CB2-selective ligand that behaves as an inverse agonist at CB2 receptors and as a weak partial agonist at CB1 receptors. L759633 and L759656 are both potent CB2-selective agonists.British Journal of Pharmacology (1999) 126, 665–672; doi:10.1038/sj.bjp.0702351
    British Journal of Pharmacology 01/2009; 126(3):665 - 672. · 5.07 Impact Factor