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 [S-35]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 [S-35]guanylyl-5'-O-(gamma-thio)-triphosphate (GTP gamma S) 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 mu- or delta-opioid receptor binding. However, comparable levels of cannabinoid- and mu- and delta-opioid-stimulated [S-35]GTP gamma S binding were observed in the caudate-putamen by [S-35]GTP gamma S autoradiography in brain sections. Scatchard analysis of net agonist-stimulated [S-35]GTP gamma S binding in membranes showed that the B-max 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.