Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.
Abstract: Selective 5-HT4 receptor agonists such as prucalopride are used as human prokinetics, since activation of 5-HT4 receptors on intestinal cholinergic neurons facilitates acetylcholine release. 5-HT4 receptors, linked to adenylyl cyclase, act via generation of cAMP. None of the 4 in vitro studies on 5-HT in horses provided evidence for neuronal 5-HT4 receptors, but none used the protocol as described in human studies [1-4]. Objective: To investigate whether functional 5-HT4 receptors are present in the equine small intestine. Methods: In vitro organ bath set up, applying electrical field stimulation (EFS) in longitudinal and circular smooth muscle strips. Results: Results were similar in both muscle layers. In the presence of 0.3 mmol/l NG-Nitro-L-arginine methyl ester and 0.3 μmol/l apamine, excluding effects of the inhibitory transmitters NO and ATP, EFS induced voltage-dependent on-contractions; these were neurogenic as they were abolished by 3 μmol/l tetrodotoxin. At a voltage inducing 50% of the maximal amplitude, the submaximal EFS-induced contractions were cholinergic as atropine (1 μmol/l) abolished them. Prucalopride (0.3 μmol/l) did not increase the amplitude of these submaximal EFS-induced contractions. Even in the presence of the nonselective phosphodiesterase inhibitor IBMX, previously shown to enhance the effect of neuronal 5-HT4 receptors by inhibiting breakdown of their 2nd messenger cAMP [5], prucalopride (3 μmol/l) had no influence. Also 5-HT (10 μmol/l), a full agonist at 5-HT4 receptors, tested in the presence of methysergide and granisetron to exclude interaction with other 5-HT receptor subtypes, did not enhance EFS-induced submaximal contractions. Conclusions: There is no evidence for presence of 5-HT4 receptors on the cholinergic neurons of the equine small intestine. These results question the application of 5-HT4 prokinetic drugs in horses. Ethical animal research: Research ethics committee oversight not currently required by this conference: the study was performed on material collected at an abattoir. Sources of funding: None. Competing interests: None declared.
© 2015 The Author(s). Equine Veterinary Journal © 2015 EVJ Ltd.
Publication Date: 2015-09-17 PubMed ID: 26376095DOI: 10.1111/evj.12486_14Google Scholar: Lookup
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- Journal Article
- Adenosine Triphosphate (ATP)
- Animal Studies
- Atropine
- Biochemistry
- Biotechnology
- Cells
- Clinical Examination
- Clinical Findings
- Clinical Pathology
- Clinical Study
- Disease Diagnosis
- Disease Treatment
- Equine Diseases
- Equine Health
- Ethics
- Gastrointestinal Health
- Horses
- In Vitro Research
- Inflammation
- Neurology
- Pharmacology
- Physiology
- Serotonin
- Veterinary Medicine
- Veterinary Research
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research conducted investigates whether a specific type of receptor for the molecule serotonin, known as 5-HT4, is present in the small intestine of horses. The study found no evidence of the receptors, questioning the effectiveness of certain drugs used for digestion in horses.
About the Study
The primary intention of the study was to find out if functional 5-HT4 receptors, associated with the release of acetylcholine, exist in the equine small intestine.
- The 5-HT4 receptor is a type of serotonin receptor. In humans, activating these receptors can stimulate acetylcholine release, enhancing intestinal movement and aiding digestion.
- The researchers examined multiple muscle layers of the equine small intestine using an in vitro organ bath setup. To this end, they applied electric field stimulation (EFS) to longitudinal and circular smooth muscle strips.
Results
The outcomes of the experiments were intriguing for both muscle layers.
- Firstly, it was noted that EFS led to the creation of neurogenic , voltage-dependent on-contractions, which were eliminated by tetrodotoxin (a potent neurotoxin).
- The researchers confirmed these contractions as cholinergic. They achieved this by observing that atropine, a known inhibitor of acetylcholine, abolished these contractions produced at a specified voltage that induced 50% of the maximal amplitude.
- Significantly, the researchers found that prucalopride, a selective 5-HT4 receptor agonist, did not increase the amplitude of these contractions. They noted this even when using IBMX, a substance known to augment the effect of neuronal 5-HT4 receptors by stopping the breakdown of cAMP, their secondary messenger.
- Even serotonin, a full agonist at 5-HT4 receptors, did not amplify submaximal contractions when tested in the presence of other serotonin receptor subtype inhibitors, further asserting the absence of 5-HT4 receptors in horse intestinal neurons.
Conclusion and Impact
Ultimately, the research found no evidence of 5-HT4 receptors present in the cholinergic neurons of the horse’s small intestine.
- This knowledge challenges traditional use of 5-HT4 prokinetic drugs for aiding digestion in horses, and as such, practices may need to be revised.
- The research adhered to ethical standards by using material collected from an abattoir, rather than from live animals.
- No external funding or competing interests were associated with the study.
Cite This Article
APA
Delesalle CJ, Callens C, Van Colen I, Lefebvre RA.
(2015).
Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.
Equine Vet J, 47 Suppl 48, 7.
https://doi.org/10.1111/evj.12486_14 Publication
Researcher Affiliations
- Ghent University, Faculty of Veterinary Medicine, Department of Comparative Physiology, Belgium.
- Ghent University, Faculty of Bioscience Engineering, Kortrijk, Belgium.
- Ghent University, Heymans Institute of Pharmacology, Faculty of Medicine and Health Sciences, Belgium.
- Ghent University, Heymans Institute of Pharmacology, Faculty of Medicine and Health Sciences, Belgium.
Citations
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