Receptor subtypes Y_1 and Y_5 mediate neuropeptide Y induced feeding in the guinea-pig

摘要

1 Neuropeptide Y (NPY) is one of the most potent stimulants of food intake. It has been debated which receptor subtype mediates this response. Initially Y_1 was proposed, but later Y_5 was announced as a 'feeding' receptor in rats and mice. Very little is known regarding other mammals. The presbnt 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. 2 PYY, (Leu~(31),Pro~(34))NPY and NPY(2 - 36) stimulated feeding, whereas NPY(13 - 36) had no effect. These data suggest that either Y_1 or Y_5 receptors or both may mediate NPY induced food intake in guinea-pigs. 3 The Y_1 receptor antagonists, BIBO 3304 and H 409/22 displayed nanomolar affinity for the Y_1 receptor (K_i values 1.1 +- 0.2 nM and 5.6 +- 0.9 nM, respectively), but low affinity for the Y_2 or Y_5 receptors. When guinea-pigs were pretreated with BIBO 3304 and H 409/22, the response to NPY was inhibited. 4 The Y_5 antagonist, CGP 71683A had high affinity for the Y_5 receptor (K_i 1.3 +- 0.05 nM) without having any significant activities at the Y_1 and Y_2 receptors. When CGP 71683A was infused into brain ventricles, the feeding response to NPY was attenuated. 5 The present study shows that NPY stimulates feeding in guinea-pigs through Y_1 and Y_5 receptors. As the guinea-pig is very distantly related to the rat and mouse, this suggests that both Y_1 and Y_5 receptors may mediate NPY-induced hyperphagia also in other orders of mammals.