Evidence for involvement of neuropeptide Y receptors in the regulation of food intake: studies with Y1-selective antagonist BIBP3226.
1. Experiments were conducted to evaluate the effects of the novel non-peptide neuropeptide Y Y1 receptor antagonist, BIBP3226 (N2-(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 Y1 and Y3 receptor agonist, [Leu31,Pro34]NPY and a Y5 receptor agonist human peptide YY3-36 (hPYY3-36, 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 [Leu31,Pro34]NPY but not that of hPYY3-36. 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 Y1 and Y5 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 Y1 receptor (possibly Y5 receptor). However, the NPY Y1 receptors may mediate the effect of endogenous NPY in conditions of increased energy demand or on intake of highly palatable diets.
Department of Pharmacology, Faculty of Medicine, University of Tartu, Estonia.
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Kask
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Rägo
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Harro
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D002149:Energy Intake; D005247:Feeding Behavior / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009478:Neuropeptide Y / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000502:physiology*; D013217:Starvation
C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D001120:Arginine; D003975:Diazepam