μオピオイドアゴニストDAMGOの受容体選択性に関与する受容体構造

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The structural basis of opioid receptors (OPRs) for the subtype-selective binding of DAMGO, a μ-opioid receptor selective agonist, was investigated using chimeric μ/δ and μ/κ-OPRs. Replacement of the region around the first extracellular loop of the δ-OPR with the corresponding region of the μ-OPR gave the resultant chimeric receptor the similar affinity for DAMGO compared with the wild-type μ-OPR, while reciprocal replacement deprived the high affinity for DAMGO from the μ-OPR. On the other hand, replacement of the region around the third extracellular loop of the μ-OPR with the corresponding region of the κ-OPR remarkably decreased the binding affinity for DAMGO, while the reciprocal chimera revealed the high affinity for DAMGO. These results indicate that DAMGO distinguishes between μ- and δ-OPRs at the region around the first extracellular loop, while the third extracellular loop is important for the distinction between μ- and κ-OPRs by DAMGO. Furthermore, displacement studies revealed that the region around the first extracellular loop is, at least in part, involved in the discrimination between μ- and δ-OPRs by peptidic μ-selective ligands, such as dermorphin, morphiceptin and CTOP, but not by non-peptidic ligands, such as morphine and naloxone. On the contrary, the region around the third extracellular loop is involved in the discrimination between μ- and κ-OPRs not only by the peptidic μ-selective ligands but also by the non-peptidic ligands.
社団法人日本薬理学会の論文
1995-09-01

μオピオイドアゴニストDAMGOの受容体選択性に関与する受容体構造

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