Ligand selectivity of cloned human and rat opioid mu receptors

Opiate receptors play major roles in analgesic and euphoric effects of opiate drugs. Recent cloning of cDNAs encoding the rodent and human μ receptor revealed high homology between the predicted receptors but also some sequence differences. To determine if these sequence differences produced significant changes in ligand-selectivity profiles, we assessed these profiles in expressing COS and CHO cell lines using the agonist ligand [¹²⁵I]IOXY-AGO (6β-[¹²⁵Iodo]-3,14-dihydroxy-17-methyl-4,5α- epoxymorphinan). This ligand's high specific activity (2,200 Ci/mmol) and high affinity for μ opioid receptors generated high signal-to-noise ratio binding. The resulting ligand-selectivity profiles of the human and rat μ receptors reveal modest differences in affinities for morphine and naloxone in COS cells but not CHO cells. Ligand-selectivity profiles of the rat and human μ receptors were otherwise similar. Interesting differences between these data and data previously obtained with the peptide agonist [³H]DAMGO suggest that the peptide and alkaloid agonists may label different domains of the μ receptor.