DAMGO, a μ‐opioid receptor selective agonist, distinguishes between μ‐ and δ‐opioid receptors around their first extracellular loops

Abstract

The structural basis of μ‐opioid receptor (OPR) for the specificity in its ligand binding was investigated using chimeric μ/δ‐OPRs. Replacement of the region around the first extracellular loop of δ‐OPR with the corresponding region of μ‐OPR gave the resultant chimeric receptor the similar affinity to DAMGO compared with the native μ‐OPR. The reciprocal replacement deprived the high affinity to DAMGO from μ‐OPR. These results indicate that the difference(s) in the structure around the first extracellular loop is critical for DAMGO to distinguish between μ‐ and δ‐OPRs. Furthermore, displacement studies revealed that this region is partly involved in the discrimination between μ‐ and δ‐OPRs by other peptidic μ‐selective ligands, such as dermorphin, morphiceptin and CTOP, but not by non‐peptidic ligands, such as morphine and naloxone.