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

• Published in: FEBS letters 1995-01, Vol.357 (1), p.93-97
• Main Authors: Onogi, Tatsuhiro, Minami, Masabumi, Katao, Yoshikazu, Nakagawa, Takayuki, Aoki, Yasuhide, Toya, Takashi, Katsumata, Seishi, Satoh, Masamichi
• Format: Article
• Language: English
• Subjects: [d-Ala, MePhe4, Gly(ol)5]enkephalin; [d-Pen2,5]enkephalin; Amino Acid Sequence; Animals; Cell Line; Chimeric receptor; Cloning, Molecular; CTOP; d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2; DAMGO; DPDPE; Enkephalin, Ala-MePhe-Gly; Enkephalins - pharmacology; extracellular loop; G-protein; GTP binding protein; Ligand binding; Molecular Sequence Data; Opioid receptor; OPR; Protein Conformation; Rats; Receptors, Opioid, delta - chemistry; Receptors, Opioid, delta - drug effects; Receptors, Opioid, mu - chemistry; Receptors, Opioid, mu - drug effects; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - drug effects; transmembrane domain; μ-type
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(94)01341-W

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.