Neuropeptide Y Induced Feeding in the Rat Is Mediated by a Novel Receptor1

There are now six recognized neuropeptide Y (NPY) receptor subtypes (Y1–Y4 and two recently cloned distinct receptors labeled Y5), of which Y1 and one of the Y5’s have been suggested could mediate the effect of NPY on feeding. The fragments NPY(2–36) and NPY(3–36), which bind Y1 only poorly, were injected intracerebroventricularly (icv) and found to have similar dose-response relationships to NPY in the stimulation of feeding. However NPY(13–36), which stimulates both Y2 and Y5, caused no increase in food intake, even at high doses. Maximal stimulation with the classical Y1 agonist[ Pro34]-NPY produced only 50% of the maximum effect of NPY itself despite fully inhibiting adenylyl cyclase activity in vitro in a Y1 system. The novel fragment[ Pro34]-NPY(3–36) is as effective at stimulating food intake as the classical Y1 analogue [Pro34]-NPY but bound to the Y1 receptor with only 1/20th of the affinity of NPY and failed to inhibit adenylyl cyclase through this receptor.[ Pro34]-NPY(3–36) is therefore a rela...