Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys

The orexigenic role of central neuropeptide Y (NPY) in nonhuman primates has been questioned. Therefore, we have studied the effect of central NPY on feeding in ad libitum-fed male rhesus macaques. NPY dose-dependently increased food intake, with the maximal effect obtained by 50 microg (960 min foo...

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Published in:The journal of clinical endocrinology and metabolism 1999-10, Vol.84 (10), p.3781-3791
Main Authors: LARSEN, P. J, TANG-CHRISTENSEN, M, STIDSEN, C. E, MADSEN, K, SMITH, M. S, CAMERON, J. L
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain - metabolism
Clonidine - pharmacology
Dose-Response Relationship, Drug
Eating - drug effects
Eating - physiology
Feeding. Feeding behavior
Fundamental and applied biological sciences. Psychology
Hydrocortisone - blood
Injections, Intraventricular
Insulin - blood
Macaca mulatta
Male
Neuropeptide Y - agonists
Neuropeptide Y - antagonists & inhibitors
Neuropeptide Y - pharmacology
Peptides, Cyclic - pharmacology
Receptors, Neuropeptide Y - antagonists & inhibitors
Receptors, Neuropeptide Y - physiology
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:The orexigenic role of central neuropeptide Y (NPY) in nonhuman primates has been questioned. Therefore, we have studied the effect of central NPY on feeding in ad libitum-fed male rhesus macaques. NPY dose-dependently increased food intake, with the maximal effect obtained by 50 microg (960 min food intake +/- SEM, 104 +/- 5 to 188 +/- 11 g; vehicle vs. NPY; n = 6). Blood glucose levels were unaffected by intracerebroventricular administration of NPY, but animals receiving either 20 or 50 microg displayed increased plasma levels of insulin and cortisol at few time points. To assess the pharmacological specificity of this response, a novel Y1 antagonist, [(Ile,Glu,Pro,Daba,Tyr,Arg,Leu,Arg,Tyr-NH2)2 cyclic (2,4'),(2',4)-diamide] (Y1ANT), was synthesized. Receptor binding experiments demonstrated that Y1ANT preferentially binds to Y1 and Y4 receptors (pKi 10.12 +/- 0.06 and 9.11 +/- 0.05 nmol/L, respectively). Functional analysis revealed that Y1ANT is a Y1 antagonist and a partial Y4 agonist. Central administration of Y1ANT blocked NPY-induced feeding. In food-deprived monkeys, Y1ANT attenuated the feeding response. However, Y1ANT had no effect on food intake in satiated monkeys. Thus, endogenous NPY is likely to be involved in the regulation of food intake in the nonhuman primate, and this effect is at least partially mediated via Y1-like receptors.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.84.10.3781