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Different domains of the ORL1 and κ‐opioid receptors are involved in recognition of nociceptin and dynorphin A
Author(s) -
Lapalu Sophie,
Moisand Christiane,
Butour Jean-Luc,
Mollereau Catherine,
Meunier Jean-Claude
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00452-9
Subject(s) - nociceptin receptor , dynorphin , receptor , chemistry , opioid peptide , opioid , dynorphin a , κ opioid receptor , opioid receptor , biochemistry
In order to gain further insight into the functional architecture of structurally related G protein‐coupled receptors, the ORL1 (nociceptin) and opioid receptors, we have constructed chimeras of ORL1 and μ‐, δ‐ and κ‐opioid receptors, and compared their binding and functional properties with those of the parent receptors. We find in particular that a ORL1–κ‐opioid (O‐K) hybrid construct has retained high affinity for non‐type‐selective opiate ligands, and has acquired the ability to bind and respond to enkephalins and μ‐ and/or δ‐opioid receptor‐selective enkephalins analogs, thus behaving like a `universal' opioid receptor. Most significantly however, whilst the ORL1 and κ‐opioid receptors display high binding preference ( K D 0.1 vs. 100 nM) for their respective endogenous ligands, nociceptin and dynorphin A, the O‐K chimeric receptor binds both nociceptin and dynorphin A, with high affinity ( K D <1 nM). Together, these data (i) add weight to the hypothesis that the extracellular loops of opioid receptors act as a filter for ligand selection, and (ii) demonstrate that different domains of the ORL1 and κ‐opioid receptors are involved in recognition of their endogenous peptide ligands.