Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/22722
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Peripheral versus central modulation of gastric vagal pathways by metabotropic glutamate receptor 5 |
Author: | Young, R. Page, A. Isaacs, N. O'Donnell, T. Blackshaw, L. |
Citation: | American Journal of Physiology: Gastrointestinal and Liver Physiology, 2007; 292(2):G501-G511 |
Publisher: | Amer Physiological Soc |
Issue Date: | 2007 |
ISSN: | 0193-1857 1522-1547 |
Statement of Responsibility: | Richard L. Young, Amanda J. Page, Tracey A. O'Donnell, Nicole J. Cooper and L. Ashley Blackshaw |
Abstract: | Metabotropic glutamate receptors (mGluR) are classified into group I, II, and III mGluR. Group I (mGluR1, mGluR5) are excitatory, whereas group II and III are inhibitory. mGluR5 antagonism potently reduces triggering of transient lower esophageal sphincter relaxations and gastroesophageal reflux. Transient lower esophageal sphincter relaxations are mediated via a vagal pathway and initiated by distension of the proximal stomach. Here, we determined the site of action of mGluR5 in gastric vagal pathways by investigating peripheral responses of ferret gastroesophageal vagal afferents to graded mechanical stimuli in vitro and central responses of nucleus tractus solitarius (NTS) neurons with gastric input in vivo in the presence or absence of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP). mGluR5 were also identified immunohistochemically in the nodose ganglia and NTS after extrinsic vagal inputs had been traced from the proximal stomach. Gastroesophageal vagal afferents were classified as mucosal, tension, or tension-mucosal (TM) receptors. MPEP (1–10 µM) inhibited responses to circumferential tension of tension and TM receptors. Responses to mucosal stroking of mucosal and TM receptors were unaffected. MPEP (0.001–10 nmol icv) had no major effect on the majority of NTS neurons excited by gastric distension or on NTS neurons inhibited by distension. mGluR5 labeling was abundant in gastric vagal afferent neurons and sparse in fibers within NTS vagal subnuclei. We conclude that mGluR5 play a prominent role at gastroesophageal vagal afferent endings but a minor role in central gastric vagal pathways. Peripheral mGluR5 may prove a suitable target for reducing mechanosensory input from the periphery, for therapeutic benefit. |
Keywords: | Esophageal Sphincter, Lower Esophagus Stomach Brain Brain Stem Medulla Oblongata Solitary Nucleus Nodose Ganglion Afferent Pathways Neurons Vagus Nerve Mechanoreceptors Animals Ferrets Pyridines Receptors, Metabotropic Glutamate Excitatory Amino Acid Antagonists Action Potentials Sensory Receptor Cells Receptor, Metabotropic Glutamate 5 |
Description: | Copyright © 2007 by the American Physiological Society. |
Provenance: | First published October 19, 2006. |
DOI: | 10.1152/ajpgi.00353.2006 |
Published version: | http://dx.doi.org/10.1152/ajpgi.00353.2006 |
Appears in Collections: | Anatomical Sciences publications Aurora harvest 2 |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.