Role of glutamatergic neurotransmission in the enteric nervous system and brain-gut axis in health and disease

Filpa, Viviana; Moro, Elisabetta; Protasoni, Marina; Crema, Francesca; Frigo, Gianmario; Giaroni, Cristina

doi:10.1016/j.neuropharm.2016.08.024

Cited by 85 publications

(84 citation statements)

References 224 publications

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“…Rather, a variety of gliotransmitters released by either, or both mechanisms (Malarkey & Parpura, 2009) could mediate them. For instance, glutamate can modulate GI motility (Filpa et al, 2016). The identity of gliotransmitter(s) utilized in EG-mediated modulation of gut physiology remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

Two modes of enteric gliotransmission differentially affect gut physiology

Grubišić

Parpura

2017

Glia

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Enteric glia (EG) in the enteric nervous system (ENS) can modulate neuronally regulated gut functions. Using molecular genetics, we assessed the effects that molecular entities expressed in EG and otherwise mediating two distinct mechanisms of gliotransmitter release, connexin 43 (Cx43) hemichannel vs. Ca2+-dependent exocytosis, have on gut function. The expression of mutated Cx43G138R (which favors hemichannel, as opposed to gap-junctional activity) in EG increased gut motility in vivo, while a knock-down of Cx43 in EG resulted in the reduction of gut motility. However, inhibition of Ca2+-dependent exocytosis in EG did not affect gut motility in vivo; rather, it increased the fecal pellet fluid content. Hampering either Cx43 expression or Ca2+-dependent exocytosis in EG had an effect on colonic migrating motor complexes, mainly decreasing frequency and velocity of contractions ex vivo. Thus, EG can differentially modulate gut reflexes using the above two distinct mechanisms of gliotransmission.

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Section: Discussionmentioning

confidence: 99%

Two modes of enteric gliotransmission differentially affect gut physiology

Grubišić

Parpura

2017

Glia

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“…The primary receptor types (T1R1 + T1R3, mGluR4, and mGluR1) are found in the stomach and intestine, and both stomach and duodenal MSG can elicit mucosal responses [56,64]. There is a large distribution and function of the major glutamate receptors along the brain gut axis [65]. Analysis of Group III mGlu receptor expression shows the presence of mGlu 4, 6, 7, and 8 receptors not only in the brain but also along the gastrointestinal tract where they are involved in several neural function and digestive processes [66].…”

Section: Glu Metabolism In the Gutmentioning

confidence: 99%

The Roles of Dietary Glutamate in the Intestine

Tomé¹

2018

Ann Nutr Metab

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Glutamate (Glu), either as one of the amino acids of protein or in free form, constitutes up to 8–10% of amino acid content in the human diet, with an intake of about 10–20 g/day in adults. In the intestine, postprandial luminal Glu concentrations can be of the order of mM and result in a high intra-mucosal Glu concentration. Glu absorbed from the intestinal lumen is for a large part metabolized by enterocytes in various pathways, including the production of energy to support intestinal motility and functions. Glu is the most important fuel for intestinal tissue, it is involved in gut protein metabolism and is the precursor of different important molecules produced within the intestinal mucosa (2-oxoglutarate, L-alanine, ornithine, arginine, proline, glutathione, γ-aminobutyric acid [GABA]). Studies in adult humans, pigs, piglets or preterm infants indicate that a large proportion of Glu is metabolized in the intestine, and that for the usual range of Glu dietary intake (bound Glu and free Glu including added Glu as a food additive in normal amounts up to 1 g/day), circulating Glu is tightly maintained at rather low concentrations. Systemic blood levels of Glu transiently rise when high doses monosodium glutamate (> 10–12 g), higher than normal human dietary consumption, are ingested and normalize within 2 h after the offset of consumption. Glu is also involved in oral and post oral nutrient chemosensing that involves gustatory nerves and both humoral and neural (vagal) gut-brain pathways with an impact on gut function and feeding behavior. Glu functions as a signaling molecule in the enteric nervous system and modulates neuroendocrine reflexes in the gastrointestinal tract. The oral taste sensation of Glu involves its binding to the oral umami taste receptors that triggers the cephalic phase response of digestion to prepare for food digestion. Glu is sensed again in the gut, inducing a visceral sensation that enhances additional gut digestive processes through the visceral sense (vago-vagal reflex).

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“…In addition, the expression of myosin light chain kinase is increased. The enteric nervous system, which can still perform its main regulatory role in vitro, regulates intestinal motility, indicating that isolated intestinal fragments can be used to study the effect and mechanism of drugs [10].…”

Section: Introductionmentioning

confidence: 99%

An Indole Alkaloid Extracted from Evodia rutaecarpa Inhibits Colonic Motility of Rats In Vitro

Wang

Xiang

Wang

et al. 2020

Gastroenterology Research and Practice

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Evodiamine (Evo) is an indole alkaloid extracted from the traditional Chinese medicinal herb Evodia rutaecarpa. Evo may regulate gastrointestinal motility, but the evidence is insufficient, and the mechanisms remain unknown. The aim of this study was to investigate the effect of Evo on colonic motility of rats and the underlying mechanisms in vitro. Rat colonic muscle was exposed to Evo (10 and 100 μM) followed by immunohistochemistry of cholecystokinin receptor 1 (CCK1R). Muscle contractions were studied in an organ bath system to determine whether CCK1R, nitric oxide (NO), and enteric neurons are involved in the relaxant effect of Evo. Whole-cell patch-clamp was used to detect L-type calcium currents (ICa,L) in isolated colonic smooth muscle cells (SMCs). CCK1R was observed in SMCs, intermuscular neurons, and mucosa of rat colon. Evo could inhibit spontaneous muscle contractions; NO synthase, inhibitor L-NAME CCK1R antagonist, could partly block this effect, while the enteric neurons may not play a major role. Evo inhibited the peak ICa,L in colonic SMCs at a membrane potential of 0 mV. The current-voltage (I–V) relationship of L-type calcium channels was modified by Evo, while the peak of the I–V curve remained at 0 mV. Furthermore, Evo inhibited the activation of L-type calcium channels and decreased the peak ICa,L. The relaxant effect of Evo on colonic muscle is associated with the inhibition of L-type calcium channels. The enteric neurons, NO, and CCK1R may be partly related to the inhibitory effect of Evo on colonic motility. This study provides the first evidence that evodiamine can regulate colonic motility in rats by mediating calcium homeostasis in smooth muscle cells. These data form a theoretical basis for the clinical application of evodiamine for treatment of gastrointestinal motility diseases.

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Role of glutamatergic neurotransmission in the enteric nervous system and brain-gut axis in health and disease

Cited by 85 publications

References 224 publications

Two modes of enteric gliotransmission differentially affect gut physiology

Two modes of enteric gliotransmission differentially affect gut physiology

The Roles of Dietary Glutamate in the Intestine

An Indole Alkaloid Extracted from Evodia rutaecarpa Inhibits Colonic Motility of Rats In Vitro

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