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

FEBS Letters

Aoki, Yasuhide²  Satoh, Masamichi²  Nakagawa, Takayuki²  Katsumata, Seishi¹  Minami, Masabumi²  Toya, Takashi¹  Katao, Yoshikazu²  Onogi, Tatsuhiro¹ 

[1] Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606-01, Japan;Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606-01, Japan

关键词: Opioid receptor;    Chimeric receptor;    Ligand binding;    μ-type;    DAMGO;    CTOP;    d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2;    DAMGO;    [d-Ala;    MePhe4;    Gly(ol)5]enkephalin;    DPDPE;    [d-Pen2;    5]enkephalin;    EL;    extracellular loop;    G-protein;    GTP binding protein;    OPR;    opioid receptor;    TM;    transmembrane domain;   

DOI  :  10.1016/0014-5793(94)01341-W

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown