Drugs acting at 5‐ HT 4, D2, motilin, and ghrelin receptors differ markedly in how they affect neuromuscular functions in human isolated stomach
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Le résumé fourni par la source
BACKGROUND: Progress in identifying safer, effective drugs to increase gastric emptying is impeded by failed clinical trials. One potential reason for failure is lack of translation from animal models to the human condition. To make progress, the actions of existing drugs and new therapeutic candidates need to be understood in human isolated stomach. METHODS: Neuromuscular activities were evoked in human gastric antrum circular muscle by electrical field stimulation (EFS), defined phenotypically using pharmacological tools. KEY RESULTS: EFS evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. The 5-HT4 receptor agonist/D2 antagonist metoclopramide and the selective 5-HT4 agonist prucalopride, facilitated contractions in the absence (respectively, Emax 95 ± 29% and 42 ± 9%, n = 3-6 each concentration) and presence (139 ± 38%, 55 ± 13%, n = 3-5) of the NO synthase inhibitor L-NAME, without affecting submaximal contractions to carbachol; the 5-HT4 antagonist SB204070 prevented facilitation by metoclopramide 100 μM (respectively, -5 (range -26 to 34) and 167 (12-1327)% in presence and absence; n = 5-6). The selective motilin receptor agonist camicinal provided considerably greater facilitation (478 (12-2080)% at 30 μM, n = 8). Domperidone (0.001-100 μM; n = 3-6) and acylated or des-acylated ghrelin (1-300 nM; n = 2-4) had no consistent activity, even with protease inhibitors. CONCLUSIONS & INFERENCES: 5-HT4 receptor agonists show different efficacies. Motilin receptor activation has greater potential to increase gastric emptying, whereas ghrelin and D2 receptor antagonism have no direct activity. Drugs stimulating human gastric motility directly can act regardless of disease mechanisms, whereas drugs without direct activity but an ability to block nausea/vomiting may be effective only if these symptoms exist.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Drugs acting at 5‐<scp>HT</scp><sub>4</sub>, D<sub>2</sub>, motilin, and ghrelin receptors differ markedly in how they affect neuromuscular functions in human isolated stomach
- Date Crossref
- 20/04/2014
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Queen Mary University of London Neurogastroenterology Group Blizard Institute Barts & pays non établi dans la noticeUniversité ou école supérieure
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Blizard Institute pays non établi dans la noticeUniversité ou école supérieure
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Homerton University Hospital Bariatric Surgery Department pays non établi dans la noticeÉtablissement de santé
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Research Triangle Park Foundation pays non établi dans la noticeOrganisation à but non lucratif
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GlaxoSmithKline (United States) pays non établi dans la noticeEntreprise
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Barts & The London School of Medicine and Dentistry Blizard Institute pays non établi dans la noticeUniversité ou école supérieure
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Academic DPU GlaxoSmithKline Research Triangle Park NC USA pays non établi dans la noticeInstitution
Neurogastroenterology Group Blizard Institute Barts & — Queen Mary University of London, Blizard Institute et Bariatric Surgery Department — Homerton University Hospital, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.