Endomorphin-1 Discriminates the μ-Opioid Receptor From the δ- and κ-Opioid Receptors by Recognizing the Difference in Multiple Regions

The Japanese Journal of Pharmacology

Takahiro Seki¹  Masamichi Satoh¹  Kyoko Sakano¹  Soichiro Ide¹  Masabumi Minami¹  Shinichiro Awamura¹ 

[1] Department of Molecular Pharmacology,Faculty of Pharmaceutical Sciences,Kyoto University,Kyoto 606-8501,Japan

关键词: Endomorphin-1;    Opioid receptor;    Chimeric receptor;    Binding selectivity;    Competitive binding assay;   

DOI  :  10.1254/jjp.83.306

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(22)Cited-By(6)Endomorphin−1 is a novel endogenous peptide that is highly selective for the μ−opioid receptor over the δ−and κ−opioid receptors.The structural basis of high selectivity of endomorphin−1 to the μ−opioid receptor was examined using chimeric receptors between μ− and δ−opioid receptors and those between μ− and κ−opioid receptors.The chimeric receptors were constructed by using restriction enzyme sites intrinsically possessed by or introduced to the μ−, δ− and κ−opioid receptor cDNAs.The junctions for the construction were located at the first intracellular loop(Bbs I site), third transmembrane domain(Afl III site)and fifth transmembrane domain(Bgl II site).The competitive binding assay using chimeric receptors revealed that the region from the Bbs I site to the Afl III site, including the first extracellular loop, contributes to the discrimination between μ− and δ−opioid receptors by endomorphin−1 more than any other regions.However, the region from the Afl III site to the Bgl II site and that from the Bgl II site to the carboxy terminal also somewhat contribute to the discrimination between μ− and δ−opioid receptors.For the discrimination between μ− and κ−opioid receptors, two regions, that is, the region from the Bbs I site to the Afl III site and that from the Bgl II site to the carboxy terminal, were shown to be important.The present results show that endomorphin−1 discriminates the μ−opioid receptor from the other two types of opioid receptors by recognizing the differences in several amino acid residues widely distributed through the receptor structure.We previously reported that DAMGO, a synthetic highly μ−selective peptide, discriminates between μ− and δ−opioid receptors by recognizing the difference in only one amino acid residue and discriminates between μ− and κ−opioid receptors by recognizing the difference in four residues localized in the restricted region.Although both endomorphin−1 and DAMGO are μ−opioid receptor selective peptides, molecular mechanisms for μ−selectivity are different between these peptides.

【 授权许可】

Unknown