Dietary glutamate: interactions with the enteric nervous system (596.1)

Abstract

Luminal glutamate concentration rises during protein digestion in the small intestine and passes the ENS during absorption. Glutamate, in the brain (CNS), is an excitatory neurotransmitter. We assessed a premise that glutamatergic signalling in the ENS recapitulates its transmitter role in the CNS. Pharmacological analysis with receptor agonists and antagonists together with immunohistochemical localization of glutamate transporters and receptors was used. Analysis focused on electrical and synaptic behavior of ENS neurons, stimulation of mucosal secretion by secretomotor neurons and muscle activity mediated by musculomotor neurons. 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 excited ENS neurons. Metabotropic glutamatergic agonists did not stimulate neurogenic mucosal chloride secretion. Neither L‐glutamate nor the metabotropic glutamatergic agonist, ACPD, changed the mean amplitude of spontaneously occurring contractions in circular or longitudinal strips of intestinal wall from guinea pig or human small intestine. Early discoveries, for glutamatergic neurotransmission in the CNS, inspired expectation that study in the ENS would yield discoveries recapitulating the CNS glutamatergic story. We found this not to be the case.Grant Funding Source: The work was supported in part by National Institutes of Health grant: NIH 2 R01 DK 037238 and a gra