Abstract
Effects of amino acid substitutions in the first extracellular loop region of the delta- and mu-opioid receptors were examined. Substitution of lysine-108 of the delta-receptor (delta K108) with asparagine improved affinity to [D-Ala2,MePhe4,Gly-ol5]enk ephalin (DAGO), a mu-selective peptide agonist, to be comparable with that of the mu-receptor. On the other hand, replacement of mN127 with lysine decreased the affinity to DAGO by approximately 15-fold. These results suggest that dK108 and mN127, which correspond to each other in the aligned amino acid sequences, mainly determine the difference in DAGO binding affinity between the delta- and mu-receptors.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Analgesics / metabolism
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Animals
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Asparagine
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Binding Sites
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Binding, Competitive
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Enkephalin, D-Penicillamine (2,5)-
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Enkephalins / metabolism*
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Kinetics
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Lysine
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Molecular Sequence Data
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Morphine / metabolism
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Mutagenesis, Site-Directed
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Protein Structure, Secondary*
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Rats
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, delta / chemistry*
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Receptors, Opioid, delta / metabolism*
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / chemistry*
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Receptors, Opioid, mu / metabolism*
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Recombinant Proteins / agonists
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
Substances
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Analgesics
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Enkephalins
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Receptors, Opioid, delta
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Receptors, Opioid, mu
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Recombinant Proteins
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Asparagine
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Morphine
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Enkephalin, D-Penicillamine (2,5)-
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Lysine