TY - JOUR T1 - Regional Differences in Cannabinoid Receptor/G-protein Coupling in Rat Brain JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1632 LP - 1642 VL - 282 IS - 3 AU - Christopher S. Breivogel AU - Laura J. Sim AU - Steven R. Childers Y1 - 1997/09/01 UR - http://jpet.aspetjournals.org/content/282/3/1632.abstract N2 - Cannabinoid receptor activation of G-proteins can be measured by WIN 55212–2-stimulated [35S]GTPγS binding. Receptor/transducer amplification factors, interpreted as the number of G-proteins activated per occupied receptor, are the ratio of the apparent Bmax of net agonist-stimulated [35S]GTPγS binding to the B maxof receptor binding. The present study examined whether amplification factors for cannabinoid receptors differ among various rat brain regions. In autoradiographic studies with [3H]WIN 55212–2 and WIN 55212–2-stimulated [35S]GTPγS binding, some regions displayed different relative levels of agonist-stimulated [35S]GTPγS binding than receptor binding. To quantify amplification factors, membranes from different brain regions were assayed by saturation binding analysis of net WIN 55212–2-stimulated [35S]GTPγS, [3H]SR141716A (antagonist) and [3H]WIN 55212–2 (agonist) binding. For [3H]SR141716A binding, amplification factors varied significantly from 2.0 (frontal cortex) to 7.5 (hypothalamus). For [3H]WIN 55212–2 binding, amplification factors ranged from 2.4 (hippocampus) to 5.5 (thalamus). Comparison of receptor binding and G-protein activation at subsaturating concentrations of WIN 55212–2 indicated that amplification factors may vary with receptor occupancy in some regions like cerebellum. Ratios between high-affinity [3H]WIN 55212–2 B max and [3H]SR141716AB max also differed significantly among brain regions. These results demonstrate that G-protein coupling by cannabinoid receptors differs among brain regions, and therefore depends on the cellular environment. The American Society for Pharmacology and Experimental Therapeutics ER -