Orphanin FQ: receptor binding and analog structure activity relationships in rat brain

Life Sci. 1996;59(1):PL23-9. doi: 10.1016/0024-3205(96)00261-5.

Abstract

A tritiated form of orphanin FQ (a heptadecapeptide also known as Nociceptin) has been prepared. This radioligand (33 Ci/mmole) was used to develop a radioreceptor assay using rat brain homogenates. Binding was observed to be saturable, and analyses of the binding data indicate the presence of a single binding site with a dissociation constant of 5 +/- 1.1 nM and Bmax of 535 +/- 85 fmoles/mg protein. Thirty-four analogues of orphanin FQ, including a complete alanine "scan" of orphanin FQ, and truncation analogues from both the N- and C- terminals were synthesized and tested. The data obtained indicate that the N-terminus plays a more critical role in binding than the C-terminus and that residues 1, 2, 4, and 8 are essential for binding.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • Brain / metabolism*
  • Dose-Response Relationship, Drug
  • Molecular Sequence Data
  • Opioid Peptides / pharmacology*
  • Radioligand Assay
  • Rats
  • Structure-Activity Relationship

Substances

  • Opioid Peptides
  • nociceptin