Differences in G-protein activation by mu- and delta-opioid, and cannabinoid, receptors in rat striatum

Receptor activation of G-proteins can be measured by agonist-stimulated [35S]GTP gamma S 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-(gamma-thio)-triphosphate (GTP gamma S) binding with the corresponding Bmax values of receptor binding in rat striatum. Scatchard analysis revealed that the Bmax of cannabinoid receptor binding was approximately ten times higher than that of mu- or delta-opioid receptor binding. However, comparable levels of cannabinoid- and mu- and delta-opioid-stimulated [35S]GTP gamma S binding were observed in the caudate-putamen by [35S]GTP gamma S autoradiography in brain sections. Scatchard analysis of net agonist-stimulated [35S]GTP gamma S binding in membranes showed that the Bmax of cannabinoid-stimulated binding was only twice that of mu- or delta-opioid-stimulated binding. Thus, the calculated amplification factors for mu- and delta-opioid receptors are seven times that of cannabinoid receptors.