Prucalopride exerts neuroprotection in human enteric neurons

American Journal of Physiology. Gastrointestinal and Liver Physiology
Francesca BiancoRoberto De Giorgio

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) and its transporters and receptors are involved in a wide array of digestive functions. In particular, 5-HT4 receptors are known to mediate intestinal peristalsis and recent data in experimental animals have shown their role in neuronal maintenance and neurogenesis. This study has been designed to test whether prucalopride, a well-known full 5-HT4 agonist, exerts protective effects on neurons, including enteric neurons, exposed to oxidative stress challenge. Sulforhodamine B assay was used to determine the survival of SH-SY5Y cells, human enteric neurospheres, and ex vivo submucosal neurons following H2O2 exposure in the presence or absence of prucalopride (1 nM). Specificity of 5-HT4-mediated neuroprotection was established by experiments performed in the presence of GR113808, a 5-HT4 antagonist. Prucalopride exhibited a significant neuroprotective effect. SH-SY5Y cells pretreated with prucalopride were protected from the injury elicited by H2O2 as shown by increased survival (73.5 ± 0.1% of neuronal survival vs. 33.3 ± 0.1%, respectively; P < 0.0001) and a significant reduction of proapoptotic caspase-3 and caspase-9 activation in all neurons tested. The protective effect of prucalopride ...Continue Reading

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Citations

May 14, 2016·Techniques in Coloproctology·M BelliniG Bassotti
Jul 28, 2016·Trends in Neurosciences·Kara Gross Margolis, Michael D Gershon
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Nov 5, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Andrew Del ColleKara Gross Margolis
May 23, 2021·Cellular and Molecular Gastroenterology and Hepatology·Pooja A ShahRobert A Cowles

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