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 m u receptor revealed high homology between the predicted receptors but also some sequence differences. To determine if these sequence differe nces produced significant changes in ligand-selectivity profiles, we a ssessed these profiles in expressing COS and CHO cell lines using the agonist ligand [I-125]IOXY-AGO (6 beta-[(125)Iodo]-3,14-dihydroxy-17-m ethyl-4,5 alpha-epoxymorphinan). This Ligand's high specific activity (2,200 Ci/mmol) and high affinity for mu opioid receptors generated hi gh signal-to-noise ratio binding. The resulting ligand-selectivity pro files of the human and rat mu receptors reveal modest differences in a ffinities for morphine and naloxone in COS cells but not CHO cells. Li gand-selectivity profiles of the rat and human mu, receptors were othe rwise similar. Interesting differences between these data and data pre viously obtained with the peptide agonist [H-3]DAMGO suggest that the peptide and alkaloid agonists may label different domains of the mu re ceptor. (C) 1995 Wiley-Liss, Inc.()