HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 577/1/295    most recent jphysiol.2006.117762v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Slattery, J. A. Articles by Blackshaw, L. A. Search for Related Content PubMed PubMed Citation Articles by Slattery, J. A. Articles by Blackshaw, L. A. Related Collections Alimentary

¹ Nerve Gut Research Laboratory, Hanson Institute, Royal Adelaide Hospital, Adelaide, Australia
² Department of Medicine
³ Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, Australia

Glutamate acts at central synapses via ionotropic (iGluR – NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed.

(Received 21 July 2006; accepted after revision 29 August 2006; first published online 31 August 2006)
Corresponding author A. J. Page: Nerve Gut Research Laboratory, Level 1, Hanson Institute, Frome Road, Adelaide, SA 5000, Australia Email: apage{at}mail.rah.sa.gov.au

This article has been cited by other articles:

				E. Scannell, C. A. Dell'Ova, E. M. Quinlan, A. D. Murphy, and N. W. Kleckner Pharmacology of ionotropic and metabotropic glutamate receptors on neurons involved in feeding behavior in the pond snail, Helisoma trivolvis J. Exp. Biol., March 1, 2008; 211(5): 824 - 833. [Abstract] [Full Text] [PDF]

				A. J. Page, J. A. Slattery, C. Milte, R. Laker, T. O'Donnell, C. Dorian, S. M. Brierley, and L. A. Blackshaw Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1376 - G1384. [Abstract] [Full Text] [PDF]