Different domains of the ORL1 and kappa-opioid receptors are involved in recognition of nociceptin and dynorphin A

FEBS Lett. 1998 May 8;427(2):296-300. doi: 10.1016/s0014-5793(98)00452-9.


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 mu-, delta- and kappa-opioid receptors, and compared their binding and functional properties with those of the parent receptors. We find in particular that a ORL1-kappa-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 mu- and/or delta-opioid receptor-selective enkephalins analogs, thus behaving like a 'universal' opioid receptor. Most significantly however, whilst the ORL1 and kappa-opioid receptors display high binding preference (KD 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 (KD < 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 kappa-opioid receptors are involved in recognition of their endogenous peptide ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Colforsin / pharmacology
  • Cricetinae
  • Cyclic AMP
  • Dynorphins / chemistry*
  • Humans
  • Kinetics
  • Ligands
  • Narcotic Antagonists / chemistry
  • Narcotics / chemistry
  • Opioid Peptides / chemistry*
  • Protein Structure, Secondary
  • Receptors, Opioid / chemistry*
  • Receptors, Opioid / genetics
  • Receptors, Opioid, kappa / chemistry*
  • Receptors, Opioid, kappa / genetics
  • Recombinant Fusion Proteins


  • Ligands
  • Narcotic Antagonists
  • Narcotics
  • Opioid Peptides
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • Recombinant Fusion Proteins
  • Colforsin
  • Dynorphins
  • nociceptin
  • nociceptin receptor
  • Cyclic AMP