title: Location of regions of the opioid receptor involved in selective agonist binding.
abstract: To elucidate which portions of the opioid receptor molecules are involved in the ligand selectivity, we have expressed chimeric receptors between the rat delta- and mu-opioid receptors from cDNAs and analysed their ligand binding properties. We demonstrate that the major binding determinant for the delta-selective enkephalin-related peptide, [D-Pen2,D-Pen5]enkephalin, resides within the region comprising the transmembrane segments V-VII and the intervening loop regions. On the other hand, the region spanning from the intracellular loop I to the amino-terminal half of the transmembrane segment III is shown to be involved in determining high-affinity binding of the mu-selective enkephalin-related peptides, [D-Ala2, MePhe4,Gly-ol5]enkephalin and [D-Ala2,MePhe4,Met-ol5]enkephalin, whereas the major determinant for binding of the mu-selective alkaloids, morphine and codeine, is demonstrated to exist in the region spanning the transmembrane segments V-VII. These results indicate that distinct regions of the opioid receptor determine the selectivity for the delta- and the mu-selective enkephalin-related peptides and that the binding determinant for the mu-selective alkaloids is distinct from that for the mu-selective enkephalin-related peptides.
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fukuda
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Mori
mesh_terms: D000818:Animals; D001665:Binding Sites; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000378:metabolism; D016314:Ethylketocyclazocine / Q000378:metabolism; D009294:Narcotics / Q000378:metabolism*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism*
chemical_list: D004745:Enkephalins; D009294:Narcotics; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D011993:Recombinant Fusion Proteins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016314:Ethylketocyclazocine; D020881:Enkephalin, D-Penicillamine (2,5)-