Activation of GABAA Receptors in Colon Epithelium Exacerbates Acute Colitis

Ma, Xiang; Sun, Qian; Sun, Xiaotong; Chen, Dawei; Wei, Chen; Yu, Xin; Liu, Chuanyong; Li, Yanqing; Li, Jingxin

doi:10.3389/fimmu.2018.00987

Cited by 53 publications

(44 citation statements)

References 46 publications

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“…Consistent with this suggestion, a recent study shows that activation of GABA A receptors in colon epithelium exacerbates acute colitis (Ma et al . ). In this context, a detailed characterization of GABA receptor subtypes associated with different functions in the GI tract may suggest a specific target to attenuate visceral pain with a limited impact on normal GI function.…”

Section: Discussionmentioning

confidence: 97%

“…), and the local immune system (Ma et al . ; Seifi et al . ), it is important to note that GABA receptor activation in the colon may also be associated with deleterious side‐effects.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the only evidence for endogenous GABA A signalling in this tissue is also in the presence of inflammation, where GABA A receptor activation of colon epithelium was shown to exacerbate inflammatory damage within the colon (Ma et al . ). Similarly, while several lines of evidence suggest GABA B receptors are present and functional in the GI tract, where GABA B agonists are not only analgesic but have shown to be an effective strategy for the attenuation of visceral hypersensitivity (Castro et al .…”

Section: Introductionmentioning

confidence: 97%

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Peripheral GABA receptors regulate colonic afferent excitability and visceral nociception

Loeza‐Alcocer

McPherson

Gold

2019

The Journal of Physiology

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Key pointsr While the presence of GABA receptors on primary afferents has been well described, most functional analyses have focused on the regulation of transmitter release from central terminals and/or signalling in the sensory neuron cell body.r Evidence that GABA receptors are transported to peripheral terminals and that there are several sources of GABA in the colon raise the possibility that GABA signalling in the periphery may influence colonic afferent excitability.r GABA A and GABA B are present and functional in the colon, where exogenous agonists decrease the excitability of colonic afferents and suppress visceral nociception.r Endogenous GABA release within the colon is sufficient to establish the resting excitability of colonic afferents as well as the behavioural response to noxious stimulation of the colon, primarily via GABA A receptors.r Peripheral GABA receptors may serve as a viable target for the treatment of visceral pain.Abstract It is well established that GABA receptors at the central terminals of primary afferent fibres regulate afferent input to the superficial dorsal horn. However, the extent to which peripheral GABA signalling may also regulate afferent input remains to be determined. The colon was used to explore this issue because of the numerous endogenous sources of GABA that have been described in this tissue. The influence of GABA signalling on colonic afferent excitability was assessed in an ex vivo mouse colorectum pelvic nerve preparation where test compounds were applied to the receptive field. The visceromotor response (VMR) evoked by noxious colorectal distension was used to assess the impact of GABA signalling on visceral nociception, where test compounds were applied directly to the colon. Application of either GABA A or GABA B receptor agonists attenuated the colonic afferent response to colon stretch. Conversely, GABA A and GABA B receptor antagonists increased the stretch response. However, while the noxious distension-induced VMR was attenuated in the presence of GABA A and GABA B receptor agonists, the VMR was only consistently increased by GABA A receptor antagonists. These results suggest Emanuel Loeza-Alcocer received his PhD in neurobiology in the laboratory of Professor Rodolfo Delgado-Lezama in Mexico City. His research was focused on characterizing the GABAergic mechanisms underlying the presynaptic inhibition of sensory neurons. At present, he investigates peripheral GABAergic inhibitory mechanisms in the colon in the group of Michael Gold PhD at University of Pittsburgh, USA. His long-term goal is to understand how peripheral GABAergic inhibition modifies sensory perception in health and disease. E. Loeza-Alcocer and others J Physiol 597.13that GABA receptors are present and functional in the peripheral terminals of colonic afferents and activation of these receptors via endogenous GABA release contributes to the establishment of colonic afferent excitability and visceral nociception. These results suggest that increasing peripheral GABA receptor signalling ...

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Section: Discussionmentioning

confidence: 97%

“…), and the local immune system (Ma et al . ; Seifi et al . ), it is important to note that GABA receptor activation in the colon may also be associated with deleterious side‐effects.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Peripheral GABA receptors regulate colonic afferent excitability and visceral nociception

Loeza‐Alcocer

McPherson

Gold

2019

The Journal of Physiology

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“…The blood sample was centrifuged at 6000 rpm for 90 seconds and the FITC-dextran concentration was measured at an excitation wavelength of 488 nm and an emission wavelength of 520 nm. 44…”

Section: Intestinal Permeabilitymentioning

confidence: 99%

Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high‐fat diet‐fed mice

Zhu

Zhang

et al. 2020

FASEB j.

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Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier, and chronic inflammation. Neohesperidin (Neo), a natural polyphenol abundant in citrus fruits, is known for its preventative and therapeutic effects on numerous diseases. Here, we report that Neo administration attenuates weight gain, low‐grade inflammation, and insulin resistance in mice fed high‐fat diet (HFD). Also, Neo administration substantially restores gut barrier damage, metabolic endotoxemia, and systemic inflammation. Sequencing of 16S rRNA genes in fecal samples revealed that Neo administration reverses HFD‐induced intestinal microbiota dysbiosis: an increase in the diversity of gut microbiota and alteration in the composition of intestinal microbiota (particularly in the relative abundances of Bacteroidetes and Firmicutes). Furthermore, systemic antibiotic treatment abolishes the beneficial effects of Neo in body weight control, suggesting that the effect of Neo on obesity attenuation largely depends on the gut microbiota. More importantly, we demonstrate that the impact of Neo on the regulation of obesity could be transferred from Neo‐treated mice to HFD‐fed mice via fecal microbiota transplantation. Collectively, our data highlight the efficacy of Neo as a prebiotic agent for attenuating obesity, implying a potential mechanism for gut microbiota mediated the beneficial effect of Neo.

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“…Luminal glutamic acid and GABA may also exert excitatory/inhibitory effects respectively on the CNS via vagus-mediated ligand–receptor interactions [ 21 ]. Of note also is the role of GABA as an enteric immunomodulator owing to its ability to regulate T cells and potentiate anti-inflammatory pathways [ 22 , 23 ]. GABA also has a key role in driving gut peristalsis [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Bioaminergic Responses in an In Vitro System Studying Human Gut Microbiota–Kiwifruit Interactions

et al. 2020

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Whole kiwifruit (‘Hayward’ and ‘Zesy002’) were examined for their bioaminergic potential after being subjected to in vitro gastrointestinal digestion and colonic fermentation. Controls included the prebiotic inulin and water, a carbohydrate-free vehicle. The dopamine precursor l-dihydroxyphenylalanine (L-DOPA) and the serotonin precursor 5-hydroxytryptophan were increased in the kiwifruit gastrointestinal digesta (‘Hayward’ > ‘Zesy002’) in comparison to the water digesta. Fermentation of the digesta with human fecal bacteria for 18 h modulated the concentrations of bioamine metabolites. The most notable were the significant increases in L-DOPA (‘Zesy002’ > ‘Hayward’) and γ-aminobutyric acid (GABA) (‘Hayward’ > ‘Zesy002’). Kiwifruit increased Bifidobacterium spp. and Veillonellaceae (correlating with L-DOPA increase), and Lachnospira spp. (correlating with GABA). The digesta and fermenta were incubated with Caco-2 cells for 3 h followed by gene expression analysis. Effects were seen on genes related to serotonin synthesis/re-uptake/conversion to melatonin, gut tight junction, inflammation and circadian rhythm with different digesta and fermenta from the four treatments. These indicate potential effects of the substrates and the microbially generated organic acid and bioamine metabolites on intestinal functions that have physiological relevance. Further studies are required to confirm the potential bioaminergic effects of gut microbiota–kiwifruit interactions.

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Activation of GABAA Receptors in Colon Epithelium Exacerbates Acute Colitis

Cited by 53 publications

References 46 publications

Peripheral GABA receptors regulate colonic afferent excitability and visceral nociception

Peripheral GABA receptors regulate colonic afferent excitability and visceral nociception

Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high‐fat diet‐fed mice

Bioaminergic Responses in an In Vitro System Studying Human Gut Microbiota–Kiwifruit Interactions

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