Cannabinoid Agonist Signal Transduction in Rat Brain: Comparison of Cannabinoid Agonists in Receptor Binding,

To investigate differences in agonist affinity, potency, and effi-cacy across rat brain regions, five representative cannabinoid compounds were investigated in membranes from three differ-ent rat brain regions for their ability to maximally stimulate [35S]guanosine-59-O-(3-thio)triphosphate (GTPgS) binding and bind to cannabinoid receptors (measured by inhibition of [3H]antagonist binding) under identical assay conditions. In all three brain regions, the rank order of potency for the stimulation of [35S]GTPgS binding and the inhibition of [3H]SR141716A binding for these compounds were identical, with CP55940 ’ levonantradol. WIN55212-2 $ D9-tetrahydrocannabinol (D9-THC). methanandamide. The rank order of efficacy was not related to potency, and relative maximal agonist effects varied across regions. Receptor binding fit to a three-site model fo