The Y1 receptor subtype mediates the cardiovascular changes evoked by NPY administered into the posterior hypothalamic nucleus of conscious rat

Document Type

Article

Publication Title

Brain Research

Abstract

An earlier study showed that the neuropeptide Y (NPY) receptor antagonist PYX-2 blocks the enhancement of a carbachol (CCh)-evoked pressor response produced by prior NPY administration into the posterior hypothalamic nucleus (PHN). The Y receptor subtype that mediates this response, and an increase in mean arterial pressure (MAP) and heart rate, remained unknown due to the lack of selectivity of PYX-2 for the Y receptor subtypes. Thus, the present study was undertaken to elucidate the Y receptor subtype responsible for mediating the NPY-evoked cardiovascular responses from the PHN by determining the rank order of potency of several NPY-related peptides for increasing MAP, and by correlating the pressor response evoked by these peptides to reported K i's and IC50's for the Y1, Y2, Y4 and Y5 receptor subtypes. The pharmacological profile (PYY≥NPY≥[Leu31,Pro34]NPY≥NPY 13-36≥hPP) and correlations suggest that the Y1 and/or Y 5 receptor subtypes mediate these cardiovascular changes. Administration of the relatively non-selective Y receptor antagonist PYX-2 or the selective Y1 receptor antagonist BIBP 3226 into the PHN prior to NPY completely blocked the cardiovascular responses. BIBP 3226 also blocked the cardiovascular changes evoked by [Leu31,Pro34]NPY, NPY13-36 and human pancreatic polypeptide (hPP). In contrast, neither BIBP 3226 nor PYX-2 inhibited the cardiovascular changes induced by peptide YY (PYY) or CCh microinjection into the PHN. These results show that NPY and PYY act on different receptors to mediate their respective cardiovascular changes from the PHN with NPY stimulating the Y1 receptor. © 2004 Elsevier B.V. All rights reserved.

First Page

11

Last Page

20

DOI

10.1016/j.brainres.2003.12.002

Publication Date

3-26-2004

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