Syndrome de l'intestin irritable

Résumé

Le syndrome de l'intestin irritable (appelé également troubles fonctionnels intestinaux, ou colopathie fonctionnelle, ou encore syndrome du côlon irritable) est une maladie chronique à symptomatologie digestive en rapport avec des modifications de la motricité et de la sensibilité de l'intestin intriquées avec des facteurs psychologiques. Le diagnostic nécessite d'éliminer les pathologies à expression similaire les plus communes. Sans gravité, cette maladie fréquente retentit sur la qualité de vie. Le traitement est symptomatique vis-à-vis des troubles digestifs, associé à une prise en charge psychologique. Le syndrome du côlon irritable touche certains humains mais peut aussi toucher certains singes. Il est classé dans les troubles gastro-intestinaux fonctionnels. Diagnostic Des critères diagnostiques ont été développés et mis à jour en 2016 (critères dits de ROME IV) :

douleur abdominale récurrente survenant en moyenne au moins 1 jour par semaine dans les 3 derniers

Source officielle

https://fr.wikipedia.org/wiki/Syndrome_de_l'intestin_irritable

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A functional variant in the alternative serotonin transporter gene SLC6A4 promoter P2 has a potential impact on irritable bowel syndrome

Christian Hammer

Wiley-Blackwell2016

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Serotonin receptor diversity in the human colon: Expression of serotonin type 3 receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E

Rudolf Hovius

Since the first description of 5-HT3 receptors more than 50 years ago, there has been speculation about the molecular basis of their receptor heterogeneity. We have cloned the genes encoding novel 5-HT3 subunits 5-HT3C, 5-HT3D, and 5-HT3E and have shown that these subunits are able to form functional heteromeric receptors when coexpressed with the 5-HT3A subunit. However, whether these subunits are actually expressed in human tissue remained to be confirmed. In the current study, we performed immunocytochemistry to locate the 5-HT3A as well as the 5-HT3C, 5-HT3D, and 5-HT3E subunits within the human colon. Western blot analysis was used to confirm subunit expression, and RT-PCR was employed to detect transcripts encoding 5-HT3 receptor subunits in microdissected tissue samples. This investigation revealed, for the first time, that 5-HT3C, 5-HT3D, and 5-HT3E subunits are coexpressed with 5-HT3A in cell bodies of myenteric neurons. Furthermore, 5-HT3A and 5-HT3D were found to be expressed in submucosal plexus of the human large intestine. These data provide a strong basis for future studies of the roles that specific 5-HT3 receptor subtypes play in the function of the enteric and central nervous systems and the contribution that specific 5-HT3 receptors make to the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome and dyspepsia. J. Comp. Neurol. 519:420-432, 2011. (C) 2010 Wiley-Liss, Inc.

Wiley-Blackwell2010

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Background Impaired 5-HT3 receptor function is likely involved in the pathogenesis of functional gastrointestinal disorders (FGID) and 5-HT3 receptor antagonists are effective treatments for chemotherapy-induced nausea and vomiting (CINV) and irritable bowel syndrome (IBS). The monoterpene alcohol menthol and the aporphine alkaloid boldine combat symptoms of gastrointestinal diseases; both interact with other members of the Cys-loop ligand-gated ion channel family and may therefore also act on 5-HT3 receptors. Methods The impact of boldine and menthol on human recombinant homomeric 5-HT(3)A- and heteromeric 5-HT(3)AB receptors in HEK293 cells was determined by radioligand binding, a luminescence-based Ca2+ assay, and a membrane potential assay. 5-HT3 protein and mRNA expression was assessed in human colon tissue. Key Results Boldine and menthol inhibited the 5-HT-induced activation of 5-HT3 receptors in the low and middle micromolar range, respectively. Boldine was a competitive antagonist of both receptors being 6.5- to 10-fold more potent at 5-HT(3)A- vs 5-HT(3)AB receptors. Menthol non-competitively and stereoselectively inhibited both receptors: In contrast to (+)-menthol, (-)-menthol was significantly more potent toward 5-HT(3)A- vs 5-HT(3)AB receptors. We show co-expression of 5-HT3A and 5-HT3B subunits in the human gut epithelium, the lamina propria, the myenteric plexus, and the muscular cell layer. Conclusions & Inferences The demonstrated 5-HT3 inhibitory effects may be relevant for boldine's and menthol's alleviating properties on FGID and may encourage clinical studies with the compounds or the plant extracts for CINV and IBS treatment. The found receptor-discriminative properties make boldine and (-)-menthol to potentially useful tools for analyzing structural differences between these receptor subtypes.

2014

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