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Eur J Pharmacol. 2009 Nov 10;622(1-3):32-6. doi: 10.1016/j.ejphar.2009.09.017. Epub 2009 Sep 17.

Enhanced effect of neuropeptide Y on food intake caused by blockade of the V(1A) vasopressin receptor.

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Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, Japan.


Food intake is regulated by various factors such as neuropeptide Y. Neuropeptide Y potently induces an increase in food intake, and simultaneously stimulates arginine-vasopressin (AVP) secretion in the brain. Recently, we reported that V(1A) vasopressin receptor-deficient (V(1A)R(-/-)) mice exhibited altered daily food intake accompanied with hyperglycemia and hyperleptinemia. Here, we further study the involvement of the AVP/V(1A) receptor in the appetite regulation of neuropeptide Y with V(1A)R(-/-) mice and antagonists for the AVP receptor. The intra-cerebral-ventricle administration of neuropeptide Y induced greater food consumption in V(1A)R(-/-) mice than wild-type (WT) mice, whereas an anorexigenic effect of leptin was not different between the two groups. This finding suggests that the orexigenic effect of neuropeptide Y was enhanced in V(1A)R(-/-) mice, leading to the increased food intake in response to the neuropeptide Y stimulation. In addition, the neuropeptide Y-induced orexigenic effect was enhanced by co-administration of OPC-21268, an antagonist for the V(1A) vasopressin receptor, into the cerebral ventricle in WT mice, whereas the neuropeptide Y-induced orexigenic effect was not affected by co-administration of SSR-149415, an antagonist for the V(1B) vasopressin receptor. These results indicate that AVP could suppress the neuropeptide Y-induced orexigenic effect via the V(1A) vasopressin receptor, and that blockade or inhibition of the AVP/V(1A) receptor signal resulted in the enhanced neuropeptide Y-induced orexigenic effect. Thus, we show that the AVP/V(1A) receptor is involved in appetite regulation as an anorexigenic factor for the neuropeptide Y-induced orexigenic effect.

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