Protective Actions of 5-HT4 Receptors in the Colonic Epithelium
Notice bibliographique
Résumé
5-HT4 receptors are expressed in colonic epithelium, and activation with 5-HT4 receptor agonists causes a number of responses, including mucus secretion from goblet cells, chloride secretion from enterocytes, and 5-HT release from enterochromaffin cells. We tested whether this receptor could serve a protective role in models of colitis and under basal conditions. Male CD-1 mice (Charles River, Canada) were administered dextran sodium sulfate (DSS; 4% w/v in tap water, MW: 40,000) or trinitrobenzene sulfonic acid (TNBS; 7.5mg/mL in 50% ethanol by enema) on day 0. Treatment with the 5-HT4 receptor agonist, tegaserod (1 mg/Kg), or agonist plus the antagonist, GR113808 (1 mg/Kg), began either 24 hours after colitis induction and continued daily for 6 days (prevention paradigm), or 5 days after colitis was induced and continued for 10 days (recovery paradigm). To test for an action of 5-HT4 receptors under basal conditions, the antagonist, GR113808 was administered to normal mice by daily enema for 10 days. Colitis was evaluated using disease activity index (DAI) and histological damage scores (HDS). Possible protective mechanisms such as improved epithelial barrier function were evaluated by cell proliferation by Ki-67 immunostaining, whereas cell migration and resistance to oxidative stress were explored in CaCo-2 cells. We also tested the effects of tegaserod and/or GR113808 on colonic motility in guinea pigs, a well described model of colonic function. Treatment with tegaserod by enema in both DSS and TNBS-inflamed animals significantly attenuated the development of colitis, and accelerated recovery from established colitis, and these effects were blocked by 5-HT4 antagonist treatment. This effect was not seen when tegaserod was administered by intraperitoneal injection. TNBS-induced dysmotility in guinea pigs was significantly reversed by 5-HT4 receptor agonist treatment, but dysmotility persisted in animals treated with the agonist plus antagonist. We observed significant increases in the proportion of epithelial cells that were Ki-67 positive in DSS-inflamed mice treated with the agonist, and this effect was blocked by the antagonist. In CaCo-2 cells, 5-HT4 receptor activation accelerated cell migration into scratches on cell cultures, and increased resistance to oxidative stress-induced apoptosis, and these effects were blocked by the antagonist. Furthermore, treatment with the antagonist alone resulted in significant increases in disease activity index, histological damage scores and bacterial translocation in mice, and led to disrupted motility patterns in guinea pig distal colon. 5-HT4 receptor stimulation reduced the development of, and accelerated the recovery from, inflammation. These effects likely involved improved wound healing and resistance to oxidative stress. Interestingly, inhibition of 5-HT4 activity in normal animals resulted in inflammation, decreased epithelial proliferation and disrupted motility. Taken together, these data suggest that activation of mucosal 5-HT4 receptors has a protective effect in the normal and the inflamed colon.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».