Dimerization of morphine and orphanin FQ/nociceptin receptors: generation of a novel opioid receptor subtype

Biochem Biophys Res Commun. 2002 Sep 27;297(3):659-63. doi: 10.1016/s0006-291x(02)02258-1.

Abstract

Although orphanin FQ/nociceptin (OFQ/N) receptors are a member of the opioid receptor family of receptors, they bind traditional opioids with very poor affinity. We now demonstrate that mu opioid receptors can physically associate with OFQ/N receptors, resulting in a complex with a unique binding selectivity profile. Immunoprecipitation of epitope-tagged OFQ/N receptors co-precipitates mu receptors. When the two receptors were co-expressed in CHO cells, [3H]OFQ/N retained its high binding affinity for its receptor. However, co-expression of the two receptors increased by up to 250-fold the affinity of a series of opioids in [3H]OFQ/N binding assays. This enhanced affinity was limited to agonists with high affinity for mu receptors. Selective kappa(1) and delta opioids did not lower binding. Despite the dramatic increase in affinity for the opioid agonists in co-expressing cells, the opioid antagonists naloxone and diprenorphine failed to compete [3H]OFQ/N binding.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cell Membrane / metabolism
  • Cloning, Molecular
  • Cricetinae
  • Dimerization
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacokinetics
  • Genetic Vectors
  • Morphine / chemistry
  • Morphine / metabolism*
  • Polymerase Chain Reaction
  • Receptors, Opioid / chemistry
  • Receptors, Opioid / genetics
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid, mu / isolation & purification
  • Receptors, Opioid, mu / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Restriction Mapping
  • Tritium

Substances

  • Receptors, Opioid
  • Receptors, Opioid, mu
  • Recombinant Proteins
  • Tritium
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Morphine
  • nociceptin receptor