Receptor subtypes Y[sub1] and Y[sub5] 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[sub1] was proposed, but later Y[sub5] 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[sup31],Pro[sup34])NPY and NPY(2-36) stimulated feeding, whereas NPY(13-36) had no effect. These data suggest that either Y[sub1] or Y[sub5] receptors or both may mediate NPY induced food intake in guinea-pigs. 3 The Y, receptor antagonists, BIBO 3304 and H 409/22 displayed nanomolar affinity for the Y[sub1] receptor (K[sub1] values 1.1 7plusmn;0.2 nM and 5.6 ±0.9 nM, respectively), but low affinity for the Y[sub2] or Y[sub5] receptors. When guinea-pigs were pretreated with BIBO 3304 and H 409/22, the response to NPY was inhibited. 4 The Y[sub5] antagonist, CGP 71683A had high affinity for the Y[sub5] receptor (K[sub1] 1.3 ±0.05 nM) without having any significant activities at the Y[sub1] and Y[sub2] 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[sup1] and Y[sub5] receptors. As the guinea-pig is very distantly related to the rat and mouse, this suggests that both Y[sub1] and Y[sub5] receptors may mediate NPY-induced hyperphagia also in other orders of mammals [ABSTRACT FROM AUTHOR]