MOLECULAR-BIOLOGY AND PHARMACOLOGY OF CLONED OPIOID RECEPTORS

The cloning and expression of DNA for the three major opioid receptor types (mu, delta, and kappa) present new research opportunities for th e characterization of opioid drugs and their interactions with these r eceptors. Genomic and cDNA clones for opioid receptors exist for sever al animal species including mouse, rat, guinea pig, and human. These i nclude clones for all three human opioid receptor types. The receptor proteins consist of about 400 amino acids and have the characteristic seven transmembrane domain structure of G-protein-coupled receptors. T here is about 60% amino acid identity between opioid receptor types an d about 90% identity between a receptor type cloned from different ani mal species. Ah opioid receptor types mediate the inhibition of adenyl yl cyclase in response to agonist binding. Radioligand binding and fun ctional studies using the cloned receptors tend to support current con clusions on opioid drug receptor selectivity and activity. Investigati ons of opioid receptor chimeras and single amino acid mutants are prov iding information on the ligand recognition sites of these receptors a nd essential support for the development of computational opioid recep tor models. A molecular model of the human delta opioid receptor is in cluded in this review.