Neuropeptide Y (NPY) is one of the most potent stimulants of food intake. It has been debated which receptor subtype mediates this response. Initially Y1 was proposed, but later Y5 was announced as a ‘feeding' receptor in rats and mice. Very little is known regarding other mammals. The present study attempts to characterize the role of NPY in feeding behaviour in the distantly related guinea-pig. When infused intracerebroventricularly, NPY dose-dependently increased food intake.PYY, (Leu31,Pro34)NPY and NPY(2 – 36) stimulated feeding, whereas NPY(13 – 36) had no effect. These data suggest that either Y1 or Y5 receptors or both may mediate NPY induced food intake in guinea-pigs.The Y1 receptor antagonists, BIBO 3304 and H 409/22 displayed nanomolar affinity for the Y1 receptor (Ki values 1.1±0.2 nM and 5.6±0.9 nM, respectively), but low affinity for the Y2 or Y5 receptors. When guinea-pigs were pretreated with BIBO 3304 and H 409/22, the response to NPY was inhibited.The Y5 antagonist, CGP 71683A had high affinity for the Y5 receptor (Ki 1.3±0.05 nM) without having any significant activities at the Y1 and Y2 receptors. When CGP 71683A was infused into brain ventricles, the feeding response to NPY was attenuated.The present study shows that NPY stimulates feeding in guinea-pigs through Y1 and Y5 receptors. As the guinea-pig is very distantly related to the rat and mouse, this suggests that both Y1 and Y5 receptors may mediate NPY-induced hyperphagia also in other orders of mammals.
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