Differences in G-protein activation by μ- and δ-opioid, and cannabinoid, receptors in rat striatum

Abstract

Receptor activation of G-proteins can be measured by agonist-stimulated [ 35S]GTPγS binding in the presence of excess guanosine diphosphate (GDP). To determine whether opioid and cannabinoid receptor-mediated G-protein activation correlate with their receptor densities, this study compared opioid- and cannabinoid-stimulated [ 35S]guanylyl-5′- O-(γ-thio)-triphosphate (GTPγS) binding with the corresponding B max values of receptor binding in rat striatum. Scatchard analysis revealed that the B max of cannabinoid receptor binding was approximately ten times higher than that of μ- or δ-opioid receptor binding. However, comparable levels of cannabinoid- and μ- and δ-opioid-stimulated [ 35S]GTPγS binding were observed in the caudate-putamen by [ 35S]GTPγS autoradiography in brain sections. Scatchard analysis of net agonist-stimulated [ 35S]GTPγS binding in membranes showed that the B max of cannabinoid-stimulated binding was only twice that of μ- or δ-opioid-stimulated binding. Thus, the calculated amplification factors for μ- and δ-opioid receptors are seven times that of cannabinoid receptors.