THE LIGAND-SELECTIVITY OF CLONED HUMAN AND RAT OPIATE MU-RECEPTORS STUDIED WITH [I-125]IOXY-AGO

The recent molecular cloning of mu, delta and kappa opiate receptors ( 1-5) has created new opportunities for the study of opiate receptors. The recent cloning of the human mu receptor (6) has shown that there i s a high homology between the predicted human and rat mu receptor sequ ences, but also some differences in sequence. We therefore sought sign ificant changes in the ligand-selectivity profile of these two recepto rs expressed in the COS and CHO cell lines under identical assay condi tions. We used the novel agonist ligand [I-125]IOXY-AGO (6 beta-[(125) Iodo]-3,14-dihydroxy-17-methyl-4,5 alpha-epoxymorphinan) since its hig h specific activity (2200 Ci/mmol) and high affinity for mu opioid rec eptors generated a high signal-to-noise ratio with use of relatively f ew expressing cells. (7). The results indicate substantial similaritie s in ligand-selectivity profile of the human and rat mu receptors, but also modest differences.