In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 310, No. 10 ( 2016-05-15), p. G768-G775
Abstract:
Serotonin (5-hydroxytryptamine, 5-HT) and its transporters and receptors are involved in a wide array of digestive functions. In particular, 5-HT 4 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-HT 4 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 H 2 O 2 exposure in the presence or absence of prucalopride (1 nM). Specificity of 5-HT 4 -mediated neuroprotection was established by experiments performed in the presence of GR113808, a 5-HT 4 antagonist. Prucalopride exhibited a significant neuroprotective effect. SH-SY5Y cells pretreated with prucalopride were protected from the injury elicited by H 2 O 2 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-HT 4 antagonist GR113808. Prucalopride promotes a significant neuroprotection against oxidative-mediated proapoptotic mechanisms. Our data pave the way for novel therapeutic implications of full 5-HT 4 agonists in gut dysmotility characterized by neuronal degeneration, which go beyond the well-known enterokinetic effect.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.00036.2016
Language:
English
Publisher:
American Physiological Society
Publication Date:
2016
detail.hit.zdb_id:
1477329-6
SSG:
12
Permalink