Neuropeptide Y induced feeding in the rat is mediated by a novel receptor

D O'Shea, DGA Morgan, K Meeran… - …, 1997 - academic.oup.com
D O'Shea, DGA Morgan, K Meeran, CMB Edwards, MD Turton, SJ Choi, MM Heath, I Gunn…
Endocrinology, 1997academic.oup.com
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 …
Abstract
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 relatively appetite-selective ligand. Coadministration of high dose NPY(13–36) and [Pro34]NPY did not enhance feeding compared with[ Pro34]-NPY alone. In addition, the NPY Y1 receptor antagonist BIBP-3226, which does not bind Y2, Y4, or Y5 receptors, significantly reduced NPY induced feeding. These results indicate that the feeding effect of icv NPY involves a novel receptor and that it is functionally distinct from the recognized receptor subtypes.
Oxford University Press