Role of neuropeptide Y Y(2) receptors in modulation of cardiac parasympathetic neurotransmission.
The aim of the study was to clarify the role of the Y(2) receptor in regulation of vagal control of the heart, using Y(2)((-/-)) receptor-knockout mice. Adult Y(2)((+/+),(-/-)) mice (50% C57BL/6-50% 129/SvJ background) were anaesthetised and artificially ventilated. Arterial blood pressure and pulse interval was recorded and both vagus nerves were cut. The cardiac end of the right vagus nerve was stimulated supra-maximally every 30 s (7 V, 2-2.5 Hz, 5 s). Neuropeptide Y (NPY) and a Y(2) receptor agonist, N-acetyl [Leu(28, 31)]NPY 24-36, were injected intravenously in both groups of mice. N-acetyl [Leu(28, 31)] NPY 24-36 was also administered to control mice in the presence of a Y(2) receptor antagonist, BIIE0246. Stimulation of the vagus nerve increased pulse interval (PI) by approximately 100 ms. NPY and N-acetyl [Leu(28, 31)] NPY 24-36 attenuated the increase in PI evoked by vagal stimulation in control mice only. The attenuation was reduced in the presence of BIIE0246. The results presented here show in Y(2)((-/-)) receptor-knockout mice that NPY and N-acetyl [Leu(28, 31)] NPY 24-36 have no effect on PI evoked by vagal stimulation. These findings demonstrate that NPY attenuates parasympathetic activity to the heart via the Y(2) receptor.
Smith-White
Margaret A
MA
Prince of Wales Medical Research Institute, Prince of Wales Hospital, Barker St., Randwick 2031, Sydney, Australia. m.smith-white@unsw.edu.au
Herzog
Herbert
H
Potter
Erica K
EK
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology / Q000601:surgery
D001552:Benzazepines; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C084653:neuropeptide Y (24-36), Ac-(Leu(28,31))-; C095889:neuropeptide Y2 receptor; D001120:Arginine; C403256:BIIE 0246