Prucalopride exerts neuroprotection in human enteric neurons

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 was reversed by the specific 5-HT4 antagonist GR113808. Prucalopride promotes a significant neuroprotection against oxidative-mediated proapoptotic mechanisms. Our data pave the way for novel therapeutic implications of full 5-HT4 agonists in gut dysmotility characterized by neuronal degeneration, which go beyond the well-known enterokinetic effect.

Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Bianco, F., Bonora, E., Natarajan, D., Vargiolu, M., Thapar, N., Torresan, F., Giancola, F., Boschetti, E., Volta, U., Bazzoli, F., Mazzoni, M., Seri, M., Clavenzani, P., Stanghellini, V., Sternini, C., De Giorgio, R. Tags: RAPID REPORT Source Type: research