In vivo inhibition of neuropeptide FF agonism by BIBP3226, an NPY Y1 receptor antagonist.
BIBP3226 {(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)-methyl]-argininamide} was recently shown to display relatively high affinities for neuropeptide FF (NPFF) receptors and exhibit antagonist activities towards NPFF receptors in vitro. The present study was undertaken to investigate the antagonistic effects of BIBP3226 on several in vivo pharmacologic profiles induced by exogenous NPFF and NPVF. (1) BIBP3226 (5 nmol) injected into the third ventricle completely antagonized the hypothermic effects of NPFF (30 nmol) and NPVF (30 nmol) after cerebral administration in mice; (2) BIBP3226 (5 nmol, i.c.v.) prevented the anti-morphine actions of NPFF (10 nmol, i.c.v.) in the mouse tail-flick assay; (3) in urethane-anaesthetized rats, both NPFF (200 nmol/kg, i.v.) and NPVF (200 nmol/kg, i.v.) increased the mean arterial blood pressure, which were significantly reduced by pretreatment with BIBP3226 (500 nmol/kg, i.v.). Collectively, these data suggest that BIBP3226, a mixed antagonist of NPY Y1 and NPFF receptors, shows in vivo antagonistic effects on NPFF receptors. In addition, it seems to be clear that the in vivo pharmacological profiles of NPFF are mediated directly by NPFF receptors.
Fang
Quan
Q
Department of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, PR China.
Guo
Jia
J
He
Feng
F
Peng
Ya-Li
YL
Chang
Min
M
Wang
Rui
R
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018013:Receptors, Neuropeptide / Q000819:agonists; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013610:Tachycardia / Q000378:metabolism; D013997:Time Factors
D014151:Anti-Anxiety Agents; C092926:BIBP 3226; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; D017476:Receptors, Neuropeptide Y; C083929:neuropeptide FF receptor; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide