Neuropeptide Y Induced Feeding in the Rat Is Mediated by a Novel Receptor1
In: Endocrinology, Jg. 138 (1997), S. 196-202
Online
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Zugriff:
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.
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Neuropeptide Y Induced Feeding in the Rat Is Mediated by a Novel Receptor1
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Autor/in / Beteiligte Person: | Gunn, I. ; Heath, M. M. ; David G.A. Morgan ; Howard, Jane K. ; Smith, David M. ; Ma, J. J. ; O'Shea, Donal ; Meeran, Karim ; Choi, S. J. ; Turton, M. D. ; Callinan, W. ; Chloe I Bloom ; Bloom, S.R. ; Small, Caroline J. ; Ghatei, M. A. ; Edwards, C. M. B. ; Taylor, G. M. ; Haddo, O. |
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Zeitschrift: | Endocrinology, Jg. 138 (1997), S. 196-202 |
Veröffentlichung: | The Endocrine Society, 1997 |
Medientyp: | unknown |
ISSN: | 1945-7170 (print) ; 0013-7227 (print) |
DOI: | 10.1210/endo.138.1.4899 |
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