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 (Susan) Smith, J. L. Cameron

    Research output: Contribution to journalArticle

    52 Citations (Scopus)

    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
    StatePublished - 1999

    Fingerprint

    Neuropeptide Y
    Macaca mulatta
    Eating
    Chemical activation
    Primates
    Haplorhini
    Diamide
    Appetite Regulation
    Functional analysis
    neuropeptide Y-Y1 receptor
    Hydrocortisone
    Blood Glucose
    Animals
    Pharmacology
    Insulin
    Plasmas
    Food
    Scanning electron microscopy

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology, Diabetes and Metabolism

    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.

    Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys. / Larsen, Philip Just; Tang-Christensen, M.; Stidsen, C. E.; Madsen, K.; Smith, M (Susan); Cameron, J. L.

    In: Journal of Clinical Endocrinology and Metabolism, Vol. 84, No. 10, 1999, p. 3781-3791.

    Research output: Contribution to journalArticle

    Larsen, PJ, Tang-Christensen, M, Stidsen, CE, Madsen, K, Smith, MS & Cameron, JL 1999, 'Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys', Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 10, pp. 3781-3791.
    Larsen, Philip Just ; Tang-Christensen, M. ; Stidsen, C. E. ; Madsen, K. ; Smith, M (Susan) ; Cameron, J. L. / Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys. In: Journal of Clinical Endocrinology and Metabolism. 1999 ; Vol. 84, No. 10. pp. 3781-3791.
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