ArticleBritish journal of pharmacology2000
An improved in vitro bioassay for the study of 5-HT(4) receptors in the human isolated large intestinal circular muscle.
Article in British journal of pharmacology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.Alimentary pharmacology & therapeutics · 2012Pooled it
- Prucalopride.Drugs · 2009Trial
- Pharmacological management of childhood constipation: Bridging today's gaps with tomorrow's therapies.World journal of clinical pediatrics · 2026Review
- Protective actions of a luminally acting 5-HTNeurogastroenterology and motility · 2023Article
- The enteric nervous system.Physiological reviews · 2023Review
- Current Opinion on Prucalopride in Gastroparesis and Chronic Constipation Treatment: A Focus on Patient Selection and Safety.Therapeutics and clinical risk management · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Cardiovascular safety of prokinetic agents: A focus on drug-induced arrhythmias.Neurogastroenterology and motility · 2018Review
- Patient considerations in the management of chronic constipation: focus on prucalopride.Patient preference and adherence · 2016Review
- Cholinergic interactions between donepezil and prucalopride in human colon: potential to treat severe intestinal dysmotility.British journal of pharmacology · 2013Article
- Review
- Article
- Pharmacology and metabolism of renzapride : a novel therapeutic agent for the potential treatment of irritable bowel syndrome.Drugs in R&D · 2008Article
- A comparison of the pharmacological properties of guinea-pig and human recombinant 5-HT4 receptors.British journal of pharmacology · 2007Article
- Article
- Prucalopride is a partial agonist through human and porcine atrial 5-HT4 receptors: comparison with recombinant human 5-HT4 splice variants.Naunyn-Schmiedeberg's archives of pharmacology · 2005Article
- Review
- Cloning, pharmacological characterisation and tissue distribution of a novel 5-HT4 receptor splice variant, 5-HT4(i).Naunyn-Schmiedeberg's archives of pharmacology · 2004Article
- Presynaptic modulation of cholinergic neurotransmission in the human proximal stomach.British journal of pharmacology · 2002Article
- 5-HT(4) receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study.British journal of pharmacology · 2001Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, it was demonstrated that 5-HT induces relaxation of human colon circular muscle through activation of 5-HT(4) receptors and 5-HT(7) receptors. The aim of the current study was to develop a new in vitro bioassay of human colon that would facilitate the pharmacological analysis of 5-HT responses mediated solely by 5-HT(4) receptors. Contracting circular muscle strips with KCl (80 mM) yielded a stable contractile tension and, in contrast to muscarinic cholinoceptor agonists and histamine, a profound reduction of spontaneous contractility. This allowed the establishment of reproducible, fully-defined, agonist concentration-response curves by cumulative dosing. Under these conditions, 5-HT induced a concentration-dependent relaxation (pEC(50) 7.31, Hill slope 0.91). Neither methysergide (10 microM) nor granisetron (1 microM) affected the 5-HT-induced relaxation, suggesting that 5-HT(1), 5-HT(2), 5-HT(3), 5-ht(5), 5-HT(6) or 5-HT(7) receptors are not involved. The lack of effect of tetrodotoxin (0.3 microM) indicated a direct effect of 5-HT on the smooth muscle. The selective 5-HT(4) receptor antagonists GR 113808, GR 125487 and RS 39604 competitively antagonized the 5-HT-induced relaxation (pK(B) 9.43, 10.12 and 8.53, respectively). SB 204070 (1 nM) produced a rightward shift (pA(2) 10.34) and depression of the 5-HT curve. These affinity estimates are similar to those previously reported for 5-HT(4) receptors. The selective 5-HT(4) receptor agonists, prucalopride and R076186, induced relaxations (pEC(50) 7.50 and 7.57, respectively), that were blocked by GR 113808 (3 nM), yielding pA(2) estimates of 9.31 and 9.21, respectively. To summarise, in KCl (80 mM)-contracted muscle strips, 5-HT induces relaxation through activation of a homogeneous smooth muscle 5-HT(4) receptor population. This new bioassay allows the focused, pharmacological characterization of human colonic 5-HT(4) receptors in vitro.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.