Bremazocine Recognizes the Difference in Four Amino Acid Residues to Discriminate Between a Nociceptin/Orphanin FQ Receptor and Opioid Receptors

[摘要] References(14)Cited-By(4)We investigated the molecular basis of the discrimination between nociceptin/orphanin FQ receptor (NociR) and opioid receptors (OPRs) by bremazocine, a non-type-selective opioid ligand. Construction of several chimeric receptors between NociR and κ-opioid receptor (KOPR) and mutant NociRs followed by binding experiments with [3H]bremazocine showed that the mutation of only four amino acid residues of NociR, Ala216, Val279, Gln280 and Val281, to the amino acid residues located at the corresponding position of KOPR, Lys227, Ile290, His291 and Ile292, made it possible for the resultant mutant NociR to bind bremazocine with high affinity. Considering that these four amino acid residues are conserved among μ-, δ- and κ-OPRs, the present result suggests that bremazocine recognizes the difference in these four amino acid residues to discriminate between NociR and OPRs.

[学科分类] 药理学

[关键词] Nociceptin/orphanin FQ receptor;Opioid receptor;Bremazocine;Chimeric receptor;Site-directed mutagenesis