Receptor subtypes Y1 and Y5 mediate neuropeptide Y induced feeding in the guinea-pig

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, was proposed, but later Y 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. 2 PYY, (Leu(31),Pro(34))NPY and NPY(2-36) stimulated feeding, whereas N-PY(13-36) had no effect. These data suggest that either Y, or Y 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, 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, and Y, 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, and Y 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.