Inhibition of neuropeptide FF (NPFF)-induced hypothermia and anti-morphine analgesia by RF9, a new selective NPFF receptors antagonist.
Neuropeptide FF (NPFF) belongs to a neuropeptide family including two precursors (pro-NPFF A and pro-NPFF B) and two receptors (NPFF1 and NPFF2). Very recently, the novel compound RF9 was reported as the truly selective antagonist on NPFF receptors. The present study examined the effects of RF9 on the hypothermia and anti-morphine action induced by NPFF in mice. (1) RF9 injected into the third ventricle was devoid of any residual agonist activity, but it completely antagonized the hypothermic effects of NPFF (30 or 45 nmol) after cerebral administration in mice; (2) RF9 did not alter the tail-flick latency and morphine analgesia in nociceptive test, however, co-administration of RF9 prevented the anti-morphine action of intracerebroventricularly applied NPFF (10 nmol, i.c.v.) in the mouse tail-flick assay. Collectively, our data indicate that RF9, behaving as a truly pure NPFF receptors antagonist, prevents NPFF-induced drops of the body temperature and morphine analgesia in mice. In addition, it further confirms that the hypothermia and anti-morphine action of NPFF are mediated directly by NPFF receptors.
Fang
Quan
Q
State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, the Hong Kong Polytechnic University, Hong Kong, PR China.
Wang
Yi-Qing
YQ
He
Feng
F
Guo
Jia
J
Guo
Jia
J
Chen
Qiang
Q
Wang
Rui
R
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009842:Oligopeptides / Q000037:antagonists & inhibitors*; D010147:Pain Measurement; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*
D000701:Analgesics, Opioid; D004151:Dipeptides; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; C508361:adamantylcarbonyl-arginyl-phenylalaninamide; C083929:neuropeptide FF receptor; D009020:Morphine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D000218:Adamantane