Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia

Lin, Mengjuan; Yu, Baoping

doi:10.2147/jpr.s164186

Cited by 7 publications

(4 citation statements)

References 43 publications

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“…Pharmacological modifications of the upregulation of HAChT have been done with ammonium pyrrolidinedithiocarbamate, which abolishes this phenomenon. Moreover, MKC-231 can enhance HAChT activity, resulting in a decrease in visceral pain [ 150 ]. Most of the investigated drugs with cholinergic effects in the treatment of IBS reduce colonic motility and stool frequency.…”

Section: Acetylcholinementioning

confidence: 99%

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Gros

Mesonero

et al. 2021

JCM

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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose aetiology is still unknown. Most hypotheses point out the gut-brain axis as a key factor for IBS. The axis is composed of different anatomic and functional structures intercommunicated through neurotransmitters. However, the implications of key neurotransmitters such as norepinephrine, serotonin, glutamate, GABA or acetylcholine in IBS are poorly studied. The aim of this review is to evaluate the current evidence about neurotransmitter dysfunction in IBS and explore the potential therapeutic approaches. IBS patients with altered colorectal motility show augmented norepinephrine and acetylcholine levels in plasma and an increased sensitivity of central serotonin receptors. A decrease of colonic mucosal serotonin transporter and a downregulation of α2 adrenoceptors are also correlated with visceral hypersensitivity and an increase of 5-hydroxyindole acetic acid levels, enhanced expression of high affinity choline transporter and lower levels of GABA. Given these neurotransmitter dysfunctions, novel pharmacological approaches such as 5-HT3 receptor antagonists and 5-HT4 receptor agonists are being explored for IBS management, for their antiemetic and prokinetic effects. GABA-analogous medications are being considered to reduce visceral pain. Moreover, agonists and antagonists of muscarinic receptors are under clinical trials. Targeting neurotransmitter dysfunction could provide promising new approaches for IBS management.

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Section: Acetylcholinementioning

confidence: 99%

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Gros

Mesonero

et al. 2021

JCM

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“…The concurrent use of multiple primary antibodies or proximity ligation assays increases detection specificity for M 3 R [72]. Other immunostaining strategies, such as those targeting ChAT, VAChT, or the choline transporter, may be appropriate if the goal is to describe the distribution of cholinergic components across a tissue that is thousands or tens of thousands of microns in length [73][74][75]. However, the expression of the machinery for ACh synthesis in a particular cell does not necessarily imply increased cholinergic signaling.…”

Section: Current Challenges and Technical Advances In The Study Of Ch...mentioning

confidence: 99%

Cholinergic Mechanisms in Gastrointestinal Neoplasia

Sampaio Moura,

Schledwitz,

Alizadeh

et al. 2024

IJMS

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Acetylcholine-activated receptors are divided broadly into two major structurally distinct classes: ligand-gated ion channel nicotinic and G-protein-coupled muscarinic receptors. Each class encompasses several structurally related receptor subtypes with distinct patterns of tissue expression and post-receptor signal transduction mechanisms. The activation of both nicotinic and muscarinic cholinergic receptors has been associated with the induction and progression of gastrointestinal neoplasia. Herein, after briefly reviewing the classification of acetylcholine-activated receptors and the role that nicotinic and muscarinic cholinergic signaling plays in normal digestive function, we consider the mechanics of acetylcholine synthesis and release by neuronal and non-neuronal cells in the gastrointestinal microenvironment, and current methodology and challenges in measuring serum and tissue acetylcholine levels accurately. Then, we critically evaluate the evidence that constitutive and ligand-induced activation of acetylcholine-activated receptors plays a role in promoting gastrointestinal neoplasia. We focus primarily on adenocarcinomas of the stomach, pancreas, and colon, because these cancers are particularly common worldwide and, when diagnosed at an advanced stage, are associated with very high rates of morbidity and mortality. Throughout this comprehensive review, we concentrate on identifying novel ways to leverage these observations for prognostic and therapeutic purposes.

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“…Moreover, the presence of the acetyl group in the ALCAR molecule can enhance cholinergic signalling by promoting the synthesis of the neurotransmitter acetylcholine, which plays an important role in both the enteric and central nervous systems [10][11][12]. Interestingly, it has been observed that acetylcholine signalling has significant antinociceptive effects in the development of visceral pain [13][14][15], so it has been proposed as a therapeutic target [16]. Cholinergic signalling is mainly attributable to the activation of the vagus nerve, which mediates a dynamic interaction between the brain and the intestine capable of containing the inflammatory response through humoral and neural signals and capable of performing an important control function even in chronic pathologies affecting the gut [17].…”

Section: Introductionmentioning

confidence: 99%

Anti-Hyperalgesic Efficacy of Acetyl L-Carnitine (ALCAR) Against Visceral Pain Induced by Colitis: Involvement of Glia in the Enteric and Central Nervous System

Lucarini,

Micheli,

Toti

et al. 2023

IJMS

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The management of abdominal pain in patients affected by inflammatory bowel diseases (IBDs) still represents a problem because of the lack of effective treatments. Acetyl L-carnitine (ALCAR) has proved useful in the treatment of different types of chronic pain with excellent tolerability. The present work aimed at evaluating the anti-hyperalgesic efficacy of ALCAR in a model of persistent visceral pain associated with colitis induced by 2,4-dinitrobenzene sulfonic acid (DNBS) injection. Two different protocols were applied. In the preventive protocol, ALCAR was administered daily starting 14 days to 24 h before the delivery of DNBS. In the interventive protocol, ALCAR was daily administered starting the same day of DNBS injection, and the treatment was continued for 14 days. In both cases, ALCAR significantly reduced the establishment of visceral hyperalgesia in DNBS-treated animals, though the interventive protocol showed a greater efficacy than the preventive one. The interventive protocol partially reduced colon damage in rats, counteracting enteric glia and spinal astrocyte activation resulting from colitis, as analyzed by immunofluorescence. On the other hand, the preventive protocol effectively protected enteric neurons from the inflammatory insult. These findings suggest the putative usefulness of ALCAR as a food supplement for patients suffering from IBDs.

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Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia

Cited by 7 publications

References 43 publications

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Cholinergic Mechanisms in Gastrointestinal Neoplasia

Anti-Hyperalgesic Efficacy of Acetyl L-Carnitine (ALCAR) Against Visceral Pain Induced by Colitis: Involvement of Glia in the Enteric and Central Nervous System

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