Biochemical evidence for orphanin FQ/nociceptin receptor heterogeneity in mouse brain

Biochem Biophys Res Commun. 1997 Jan 13;230(2):462-5. doi: 10.1006/bbrc.1996.5867.

Abstract

A recently identified novel peptide, orphanin FQ/nociceptin (OFQ/N), is an endogenous ligand for a unique member of the cloned opioid receptor family. Saturation studies in mouse brain membranes reveal curvilinear Scatchard plots with both a higher (KD 3.8 pM, Bmax 31.6 fmol/mg protein) and a lower (KD 896 pM, Bmax 233 fmol/mg protein) affinity site in brain tissue, compared to only a single site in transfected CHO cells (KD 36 pM). Competition studies confirm the high affinity of OFQ/N for this site, but shallow Hill slopes suggest heterogeneity. Traditional opioids have poor affinity for this receptor and OFQ/N and its fragments do not label traditional opioid receptors. In brain homogenates, both OFQ/N and OFQ/N(1-11) inhibit forskolin-stimulated camp accumulation with IC50 values of 1 nM or less, an action which is readily reversed by opioid antagonists. OFQ/N(1-7) shows little activity. Together, these studies suggest the presence of heterogeneous, functionally active OFQ/N receptors in mouse brain.

Publication types

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

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / metabolism*
  • CHO Cells
  • Cell Membrane / metabolism
  • Cricetinae
  • Dynorphins / pharmacology
  • Enkephalins / pharmacology
  • Kinetics
  • Mice
  • Narcotics / pharmacology
  • Opioid Peptides / metabolism*
  • Opioid Peptides / pharmacology
  • Radioligand Assay
  • Receptors, Opioid / metabolism*
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • Enkephalins
  • Narcotics
  • Opioid Peptides
  • Receptors, Opioid
  • Recombinant Proteins
  • Dynorphins
  • nociceptin
  • nociceptin receptor