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Repeated otilonium bromide administration prevents neurotransmitter changes in colon of rats underwent to wrap restraint stress

Otilonium bromide (OB) is a spasmolytic drug successfully used for the treatment of irritable bowel syndrome (IBS). Its efficacy has been attributed to the block of L‐ and T‐type Ca(2+) channels and muscarinic and tachykinin receptors in the smooth muscle. Furthermore, in healthy rats, repeated OB a...

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Detalles Bibliográficos
Autores principales: Traini, Chiara, Evangelista, Stefano, Girod, Vincent, Faussone‐Pellegrini, Maria Simonetta, Vannucchi, Maria Giuliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345670/
https://www.ncbi.nlm.nih.gov/pubmed/27866394
http://dx.doi.org/10.1111/jcmm.13016
Descripción
Sumario:Otilonium bromide (OB) is a spasmolytic drug successfully used for the treatment of irritable bowel syndrome (IBS). Its efficacy has been attributed to the block of L‐ and T‐type Ca(2+) channels and muscarinic and tachykinin receptors in the smooth muscle. Furthermore, in healthy rats, repeated OB administration modified neurotransmitter expression and function suggesting other mechanisms of action. On this basis, we investigated whether repeated OB treatment prevented the functional and neurochemical changes observed in the colon of rats underwent to wrap restrain stress (WRS) a psychosocial stressor considered suitable to reproduce the main IBS signs and symptoms. In control, WRS and OB/WRS rats functional parameters were measured in vivo and morphological investigations were done ex vivo in the colon. The results showed that OB counteracts most of the neurotransmitters changes caused by WRS. In particular, the drug prevents the decrease in SP‐, NK1r‐, nNOS‐, VIP‐, and S100β‐immunoreactivity (IR) and the increase in CGRP‐, and CRF1r‐IR. On the contrary, OB does not affect the increase in CRF2r‐IR neurons observed in WRS rats and does not interfere with the mild mucosal inflammation due to WRS. Finally, OB per se increases the Mr2 expression in the muscle wall and decreases the number of the myenteric ChAT‐IR neurons. Functional findings show a significantly reduction in the number of spontaneous abdominal contraction in OB treated rats. The ability of OB to block L‐type Ca(2+) channels, also expressed by enteric neurons, might represent a possible mechanism through which OB exerts its actions.