J Neurogastroenterol Motil.  2014 Jan;20(1):41-53.

Dietary Glutamate: Interactions With the Enteric Nervous System

• Wang GD
• Wang XY
• Xia Y
• Wood JD

Abstract

BACKGROUND/AIMS
Digestion of dietary protein elevates intraluminal concentrations of glutamate in the small intestine, some of which gain access to the enteric nervous system (ENS). Glutamate, in the central nervous system (CNS), is an excitatory neurotransmitter. A dogma that glutamatergic neurophysiology in the ENS recapitulates CNS glutamatergic function persists. We reassessed the premise that glutamatergic signaling in the ENS recapitulates its neurotransmitter role in the CNS.
METHODS
Pharmacological analysis of actions of receptor agonists and antagonists in concert with immunohistochemical localization of glutamate transporters and receptors was used. Analysis focused on intracellularly-recorded electrical and synaptic behavior of ENS neurons, on stimulation of mucosal secretion by secretomotor neurons in the submucosal plexus and on muscle contractile behavior mediated by musculomotor neurons in the myenteric plexus.
RESULTS
Immunoreactivity for glutamate was expressed in ENS neurons. ENS neurons expressed immunoreactivity for the EAAC-1 glutamate transporter. Neither L-glutamate nor glutamatergic receptor agonists had excitatory actions on ENS neurons. Metabotropic glutamatergic receptor agonists did not directly stimulate neurogenic mucosal chloride secretion. Neither L-glutamate nor the metabotropic glutamatergic receptor agonist, aminocyclopentane-1,3-dicarboxylic acid (ACPD), changed the mean amplitude of spontaneously occurring contractions in circular or longitudinal strips of intestinal wall from either guinea pig or human small intestinal preparations.
CONCLUSIONS
Early discoveries, for excitatory glutamatergic neurotransmission in the CNS, inspired enthusiasm that investigation in the ENS would yield discoveries recapitulating the CNS glutamatergic story. We found this not to be the case.

Keyword

Intestines; Motility; Proteolysis; Receptors, glutamate; Secretion

MeSH Terms

Amino Acid Transport System X-AG
Animals
Central Nervous System
Dietary Proteins
Digestion
Enteric Nervous System*
Glutamic Acid*
Guinea Pigs
Humans
Intestine, Small
Intestines
Muscles
Myenteric Plexus
Neurons
Neurophysiology
Neurotransmitter Agents
Proteolysis
Receptors, Glutamate
Submucous Plexus
Synaptic Transmission
Amino Acid Transport System X-AG
Dietary Proteins
Glutamic Acid
Neurotransmitter Agents
Receptors, Glutamate