Nature 382, 168 - 171 (11 July 1996); doi:10.1038/382168a0

A receptor subtype involved in neuropeptide-Y-induced food intake

Christophe Gerald^*, Mary W. Walker^*, Leoluca Criscione^†, Eric L. Gustafson^*, Christine Batzl-Hartmann^†, Kelli E. Smith^*, Pierre Vaysse^*, Margaret M. Durkin^*, Thomas M. Laz^*, David L. Linemeyer^*, Andrea O. Schaffhauser^†, Steven Whitebread^†, Karl G. Hofbauer^†, Robert I. Taber^*, Theresa A. Branchek^* & Richard L. Weinshank^*

^* Synaptic Pharmaceutical Corporation, 215 College Road, Paramus, New Jersey 07652-1431, USA
^† Ciba-Geigy Limited, Pharmaceutical Division, Metabolic Risk Factor Department, CH-4002 Basle, Switzerland

NEUROPEPTIDE Y (NPY) is a powerful stimulant of food intake and is proposed to activate a hypothalamic 'feeding' receptor distinct from previously cloned Y-type receptors¹. This receptor was first suggested to explain a feeding response to NPY and related peptides, including NPY 2–36, that differed from their activities at the Yl receptor². Here we report the expression cloning of a novel Y-type receptor from rat hypothalamus, which we name Y5. The complementary DNA encodes a 456-amino-acid protein with less than 35% overall identity to known Y-type receptors. The messenger RNA is found primarily in the central nervous system, including the paraventricular nucleus of the hypothalamus. The extent to which selected peptides can inhibit adenylate cyclase through the Y5 receptor and stimulate food intake in rats correspond well. Our data support the idea that the Y5 receptor is the postulated 'feeding' receptor, and may provide a new method for the study and treatment of obesity and eating disorders.

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