Opposing interplay between Neuropeptide FF and nitric oxide in antinociception and hypothermia.
This study examined the ability of the anti-opioid Neuropeptide FF (NPFF) to modify the endogenous activity of nitric oxide (NO). Antinociceptive and hypothermic effects of 1DMe (D.Tyr-Leu-(n.Me)Phe-Gln-Pro-Gln-Arg-Phe-NH(2)), an NPFF agonist, and of L-NAME (N(omega)nitro-L-arginine methyl ester), an inhibitor of nitric oxide synthase, were investigated in mice. Intraperitoneal (i.p.) injection of L-NAME induced, in the hot plate test, a dose-dependent antinociception not reversed by naloxone, an opioid antagonist, but inhibited by L-Arg, the NO synthesis precursor. Intracerebroventricular (i.c.v.) injections of 1DMe inhibit the antinociceptive activity of L-NAME in a dose-dependent manner. On the contrary, L-NAME markedly potentiated hypothermia induced by 1DMe injected in the third ventricle. These data show that Neuropeptide FF receptors exert a dual effect on endogenous NO functions and could modulate pain transmission independently of opioids.
Zajac
J M
JM
Institut de Pharmacologie et Biologie Structurale, CNRS 205 route de Narbonne 31077 cedex, Toulouse, France.
Latapie
J P
JP
Francés
B
B
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D001120:Arginine / Q000494:pharmacology; D001831:Body Temperature; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism; D007035:Hypothermia / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000378:metabolism* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy*; D013696:Temperature
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D009292:Narcotic Antagonists; D009842:Oligopeptides; D009569:Nitric Oxide; D009270:Naloxone; D009020:Morphine; D001120:Arginine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D019331:NG-Nitroarginine Methyl Ester