DAMGO, a μ‐opioid receptor selective ligand, distinguishes between μ‐and κ‐opioid receptors at a different region from that for the distinction between μ‐ and δ‐opioid receptors

FEBS Letters

Aoki, Yasuhide²  Satoh, Masamichi²  Nakagawa, Takayuki¹  Katsumata, Seishi¹  Minami, Masabumi²  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;    κ-Type;    [d-Ala2;    MePhe4;    Gly(ol)5]Enkephalin;    CTOP;    d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2;    DAMGO;    [d-Ala2;    MePhe4;    Gly(ol)5]en kephalin;    G protein;    GTP binding protein;    OPR;    opioid receptor;   

DOI  :  10.1016/0014-5793(95)00340-F

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The structural basis of opioid receptors (OPRs) for the subtype-selective binding of DAMGO, a μ-opioid receptor selective ligand, was investigated using chimeric μ/κ-OPRs. Replacement of the region from the middle of the fifth transmembrane domain to the C-terminal of μ-OPR with the corresponding region of μ-OPR remarkably decreased the binding affinity to DAMGO, while the reciprocal chimera revealed the high affinity to DAMGO. These results indicate that DAMGO distinguishes between μ- and μ-OPRs at the region around the third extracellular loop, different from the case of the distinction between μ-and δ-OPRs in which the region around the first extracellular loop is important. Furthermore, displacement studies revealed that the region around the third extracellular loop is involved in the discrimination between μ- and κ-OPRs not only by peptidic μ- selective ligands but also by non-peptidic ligands, such as morphine and naloxone.

【 授权许可】

Unknown