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Is There Evidence for Functional 5‐Hydroxytryptamine 4 (5‐ HT 4 ) Receptors in the Equine Jejunum? An In Vitro Study to Explore Options for Use of Human Prokinetic Drugs, Acting as 5‐ HT 4 Receptors, in Horses
Author(s) -
Delesalle C.J.G.,
Callens C.,
Van Colen I.,
Lefebvre R.A.
Publication year - 2015
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/evj.12486_14
Subject(s) - receptor , adenylyl cyclase , endocrinology , 5 ht receptor , medicine , cholinergic , serotonin , acetylcholine , stimulation , chemistry , biology
Reasons for performing study Selective 5‐ HT 4 receptor agonists such as prucalopride are used as human prokinetics, since activation of 5‐ HT 4 receptors on intestinal cholinergic neurons facilitates acetylcholine release. 5‐ HT 4 receptors, linked to adenylyl cyclase, act via generation of c AMP . None of the 4 in vitro studies on 5‐ HT in horses provided evidence for neuronal 5‐ HT 4 receptors, but none used the protocol as described in human studies [1–4]. Objectives To investigate whether functional 5‐ HT 4 receptors are present in the equine small intestine. Study design and 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 ‐ N itro‐ 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‐ HT 4 receptors by inhibiting breakdown of their 2nd messenger c AMP [5], prucalopride (3 μmol/l) had no influence. Also 5‐ HT (10 μmol/l), a full agonist at 5‐ HT 4 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‐ HT 4 receptors on the cholinergic neurons of the equine small intestine. These results question the application of 5‐ HT 4 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.