title: Neuropeptide Y induced feeding in the rat is mediated by a novel receptor.
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.
authors.affiliation: Department of Medicine, Hammersmith Hospital, Royal Postgraduate Medical School, London, United Kingdom.
authors.forename: D
authors.initials: D
authors.lastname: O'Shea
authors.forename: D G
authors.initials: DG
authors.lastname: Morgan
authors.forename: K
authors.initials: K
authors.lastname: Meeran
authors.forename: C M
authors.initials: CM
authors.lastname: Edwards
authors.forename: M D
authors.initials: MD
authors.lastname: Turton
authors.forename: S J
authors.initials: SJ
authors.lastname: Choi
authors.forename: M M
authors.initials: MM
authors.lastname: Heath
authors.forename: I
authors.initials: I
authors.lastname: Gunn
authors.forename: G M
authors.initials: GM
authors.lastname: Taylor
authors.forename: J K
authors.initials: JK
authors.lastname: Howard
authors.forename: C I
authors.initials: CI
authors.lastname: Bloom
authors.forename: C J
authors.initials: CJ
authors.lastname: Small
authors.forename: O
authors.initials: O
authors.lastname: Haddo
authors.forename: J J
authors.initials: JJ
authors.lastname: Ma
authors.forename: W
authors.initials: W
authors.lastname: Callinan
authors.forename: D M
authors.initials: DM
authors.lastname: Smith
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004435:Eating / Q000187:drug effects*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000502:physiology*
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D000262:Adenylyl Cyclases