Anti-analgesia of a selective NPFF2 agonist depends on opioid activity.
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.
Roussin
Anne
A
Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 Route de Narbonne, 31077 Toulouse Cedex, France.
Serre
Fuschia
F
Gouardères
Christine
C
Mazarguil
Honoré
H
Roumy
Michel
M
Mollereau
Catherine
C
Zajac
Jean-Marie
JM
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D006801:Humans; D007276:Injections, Intraventricular; D051379:Mice; D015335:Molecular Probes; D011976:Receptors, Muscarinic / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction
D000701:Analgesics, Opioid; D015335:Molecular Probes; D011976:Receptors, Muscarinic; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor