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Evidence for involvement of neuropeptide Y receptors in the regulation of food intake: studies with Y 1 ‐selective antagonist BIBP3226
Author(s) -
Kask Ants,
Rägo Lembit,
Harro Jaanus
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701969
Subject(s) - neuropeptide y receptor , orexigenic , endocrinology , medicine , agonist , hypothalamus , receptor , antagonist , chemistry , peptide yy , neuropeptide , biology
1 Experiments were conducted to evaluate the effects of the novel non‐peptide neuropeptide Y Y 1 receptor antagonist, BIBP3226 (N 2 ‐(diphenylacetyl)‐N‐[(4‐hydroxy‐phenyl)methyl]‐ d ‐arginine amide) on spontaneous, fasting‐induced and NPY‐induced food intake in rats. In addition to consumption of regular chow, the effects of BIBP3226 on consumption of highly palatable sweetened mash were monitored in a 1 h test on first exposure and after familiarization with novel food. 2 BIBP3226 (10.0 nmol, i.c.v.) had no effect on the consumption of regular chow, but reduced significantly the intake of highly palatable diet and the food intake stimulated by fasting (24 h). Neuropeptide Y (NPY, 1.0 nmol, i.c.v.) significantly increased the consumption of regular rat chow. This orexigenic effect of NPY was blocked by BIBP3226 (10.0 nmol, administered i.c.v. 5 min before NPY) at 30 min and 4 h, but not at 1 and 2 h. When animals were pretreated with diazepam (0.5 mg kg −1 , i.p., 20 min before NPY), BIBP3226 failed to suppress NPY‐induced feeding. 3 An NPY Y 1 and Y 3 receptor agonist, [Leu 31 ,Pro 34 ]NPY and a Y 5 receptor agonist human peptide YY 3–36 (hPYY 3–36 , both 30 pmol), microinjected into the paraventricular nucleus of the hypothalamus (PVN) increased the consumption of regular rat chow. BIBP3226 (0.4 nmol, into the PVN) completely blocked the stimulatory effect of [Leu 31 ,Pro 34 ]NPY but not that of hPYY 3–36 . BIBP3226 (0.4 nmol) alone failed to modify the consumption of the regular chow. Higher doses of BIBP3226 (1.0 and 2.0 nmol) injected into the vicinity of the PVN reduced the consumption of the sweetened mash. 4 These results suggest that both the NPY Y 1 and Y 5 receptors in the PVN are involved in the regulation of food intake. The stimulatory effect of exogenous NPY is probably mediated through an NPY receptor subtype that is not identical with the Y 1 receptor (possibly Y 5 receptor). However, the NPY Y 1 receptors may mediate the effect of endogenous NPY in conditions of increased energy demand or on intake of highly palatable diets.British Journal of Pharmacology (1998) 124 , 1507–1515; doi: 10.1038/sj.bjp.0701969