Anti-analgesia of a selective NPFF2 agonist depends on opioid activity

Biochem Biophys Res Commun. 2005 Oct 14;336(1):197-203. doi: 10.1016/j.bbrc.2005.08.060.


NPFF agonists designed to be selective NPFF(2) receptor probes were synthesized. D.Asn-Pro-(N-Me)Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH(2) (dNPA) displays a very high affinity (0.027nM) for NPFF(2) receptors transfected in CHO cells, and a very high selectivity with a discrimination ratio greater than 100 versus NPFF(1) receptors. dNPA acts as a potent and selective agonist in [(35)S]GTPgammaS binding experiments and inhibits intracellular cAMP production with the same efficacy as NPA-NPFF. In SH-SY5Y cells expressing NPFF(2) receptors dNPA, in the presence of carbachol, stimulates Ca(2+) release from the intracellular stores. In vivo, after intracerebroventricular injection dNPA increases body temperature in mice and reverses the morphine-induced analgesia. Also, dNPA displays anti-opioid activity after systemic administration. So far, dNPA exhibits the highest affinity and selectivity for NPFF(2) receptors and reveals that its behavioral anti-opioid activity depends on the degree of opioid-induced analgesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Body Temperature
  • Brain / metabolism
  • CHO Cells
  • Cell Line, Tumor
  • Cricetinae
  • Humans
  • Injections, Intraventricular
  • Mice
  • Molecular Probes
  • Receptors, Muscarinic / metabolism
  • Receptors, Neuropeptide / agonists*
  • Receptors, Neuropeptide / metabolism
  • Signal Transduction


  • Analgesics, Opioid
  • Molecular Probes
  • Receptors, Muscarinic
  • Receptors, Neuropeptide
  • neuropeptide FF receptor