The ligand-selectivity of cloned human and rat opiate mu receptors studied with [125I]IOXY-AGO

Abstract The recent molecular cloning of μ, δ and κ opiate receptors (1–5) has created new opportunities for the study of opiate receptors. The recent cloning of the human μ receptor (6) has shown that there is a high homology between the predicted human and rat μ receptor sequences, but also some differences in sequence. We therefore sought significant changes in the ligand-selectivity profile of these two receptors expressed in the COS and CHO cell lines under identical assay conditions. We used the novel agonist ligand [ 125 I]IOXY-AGO (6β-[ 125 Iodo]-3,14-dihydroxy-17-methyl-4,5α-epoxymorphinan) since its high specific activity (2200 Ci/mmol) and high affinity for μ opioid receptors generated a high signal-to-noise ratio with use of relatively few expressing cells. (7). The results indicate substantial similarities in ligand-selectivity profile of the human and rat μ receptors, but also modest differences.