The Y1 receptor subtype mediates the cardiovascular changes evoked by NPY administered into the posterior hypothalamic nucleus of conscious rat.
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 IC(50)'s for the Y(1), Y(2), Y(4) and Y(5) receptor subtypes. The pharmacological profile (PYY>or=NPY>or=[Leu(31),Pro(34)]NPY>or=NPY(13-36)>or=hPP) and correlations suggest that the Y(1) and/or Y(5) receptor subtypes mediate these cardiovascular changes. Administration of the relatively non-selective Y receptor antagonist PYX-2 or the selective Y(1) receptor antagonist BIBP 3226 into the PHN prior to NPY completely blocked the cardiovascular responses. BIBP 3226 also blocked the cardiovascular changes evoked by [Leu(31),Pro(34)]NPY, NPY(13-36) 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 Y(1) receptor.
Department of Pharmacology, Kirksville College of Osteopathic Medicine, A T Still University of Health Sciences, 800 W. Jefferson Street Kirksville, MO 63501, USA. jmartin@kcom.edu
John R
JR
Martin
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003243:Consciousness / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007034:Hypothalamus, Posterior / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000502:physiology*; D013552:Swine
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor