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

Philip Just Larsen, M. Tang-Christensen, C. E. Stidsen, K. Madsen, M. S. Smith, J. L. Cameron

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    Abstract

    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 libitumfed male rhesus macaques. NPY dose-dependently increased food intake, with the maximal effect obtained by 50 μg (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 μg 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] (Y1(ANT)), was synthesized. Receptor binding experiments demonstrated that Y1(ANT) preferentially binds to Y1 and Y4 receptors (pK(i) 10.12 ± 0.06 and 9.11 ± 0.05 nmol/L, respectively). Functional analysis revealed that Y1(ANT) is a Y1 antagonist and a partial Y4 agonist. Central administration of Y1(ANT) blocked NPY-induced feeding. In food-deprived monkeys, Y1(ANT) attenuated the feeding response. However, Y1(ANT) 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.

    Original languageEnglish (US)
    Pages (from-to)3781-3791
    Number of pages11
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume84
    Issue number10
    DOIs
    StatePublished - Jan 1 1999

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    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Biochemistry
    • Endocrinology
    • Clinical Biochemistry
    • Biochemistry, medical

    Cite this

    Larsen, P. J., Tang-Christensen, M., Stidsen, C. E., Madsen, K., Smith, M. S., & Cameron, J. L. (1999). Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys. Journal of Clinical Endocrinology and Metabolism, 84(10), 3781-3791. https://doi.org/10.1210/jc.84.10.3781