Part of our work is characterizing the major types of opioid receptors, mu, delta, and kappa. We showed that the binding proteins of these receptors can be separated by size; we also purified to homogeneity the mu binding site from bovine brain and have cloned this receptor. We reconstituted the mu binding protein, purifies from bovine brain in liposomes with G-protein, resulting in the restoration of selective, GTP-sensitive, high affinity mu agonist binding, and mu-specific stimulation of GTPase activity.

We also study receptor regulation by phosphorylation and sequestration, the nature of the sugar moieties of this glycoprotein and, by quantitative autoradiography, pathophysiological changes in opioid receptors. The cloning of the major opioid receptors makes available cDNA for studies, including determining regions involved in receptor activation and G-protein coupling, by site-directed mutagenesis and regulation of receptor gene expression, by in situ hybridization. Proteins that intertact with the carboxyl tail of the mu opioid receptor are under study. We also have an active program on opioid signaling via the MAP kinase pathway.