Cargando…

Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis

BACKGROUND: The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may imp...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Yan-Rong, Li, Yan, Jin, Yuan, Xu, Mang, Fan, Hong-Wei, Zhang, Qian, Tan, Guo-He, Chen, Jing, Li, Yun-Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367233/
https://www.ncbi.nlm.nih.gov/pubmed/36157548
http://dx.doi.org/10.3748/wjg.v28.i29.3854
_version_ 1784765742453882880
author Li, Yan-Rong
Li, Yan
Jin, Yuan
Xu, Mang
Fan, Hong-Wei
Zhang, Qian
Tan, Guo-He
Chen, Jing
Li, Yun-Qing
author_facet Li, Yan-Rong
Li, Yan
Jin, Yuan
Xu, Mang
Fan, Hong-Wei
Zhang, Qian
Tan, Guo-He
Chen, Jing
Li, Yun-Qing
author_sort Li, Yan-Rong
collection PubMed
description BACKGROUND: The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC. AIM: To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model. METHODS: Male rats (n = 8/each group) were randomly divided into a control (CG), a UC group (EG1), a UC + thrombin derived polypeptide 508 trifluoroacetic acid (TP508TFA; an NOS agonist) group (EG2), and a UC + NG-monomethyl-L-arginine monoacetate (L-NMMA; an NOS inhibitor) group (EG3). UC was induced by administering 5.5% DSS in drinking water without any other treatment (EG1), while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA, respectively. The disease activity index (DAI) and histological assessment were recorded for each group, whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining, Western blot, and enzyme linked immunosorbent assay, respectively. In addition, the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system. RESULTS: The proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1, EG2, and EG3 than in the CG group. Compared with the EG1, the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated, respectively. Thus, during UC, regulation of the expression of NOS within the MP improved the intestinal motility, thereby favoring the recovery of intestinal functions. CONCLUSION: In UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.
format Online
Article
Text
id pubmed-9367233
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Baishideng Publishing Group Inc
record_format MEDLINE/PubMed
spelling pubmed-93672332022-09-23 Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis Li, Yan-Rong Li, Yan Jin, Yuan Xu, Mang Fan, Hong-Wei Zhang, Qian Tan, Guo-He Chen, Jing Li, Yun-Qing World J Gastroenterol Basic Study BACKGROUND: The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC. AIM: To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model. METHODS: Male rats (n = 8/each group) were randomly divided into a control (CG), a UC group (EG1), a UC + thrombin derived polypeptide 508 trifluoroacetic acid (TP508TFA; an NOS agonist) group (EG2), and a UC + NG-monomethyl-L-arginine monoacetate (L-NMMA; an NOS inhibitor) group (EG3). UC was induced by administering 5.5% DSS in drinking water without any other treatment (EG1), while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA, respectively. The disease activity index (DAI) and histological assessment were recorded for each group, whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining, Western blot, and enzyme linked immunosorbent assay, respectively. In addition, the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system. RESULTS: The proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1, EG2, and EG3 than in the CG group. Compared with the EG1, the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated, respectively. Thus, during UC, regulation of the expression of NOS within the MP improved the intestinal motility, thereby favoring the recovery of intestinal functions. CONCLUSION: In UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients. Baishideng Publishing Group Inc 2022-08-07 2022-08-07 /pmc/articles/PMC9367233/ /pubmed/36157548 http://dx.doi.org/10.3748/wjg.v28.i29.3854 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
spellingShingle Basic Study
Li, Yan-Rong
Li, Yan
Jin, Yuan
Xu, Mang
Fan, Hong-Wei
Zhang, Qian
Tan, Guo-He
Chen, Jing
Li, Yun-Qing
Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis
title Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis
title_full Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis
title_fullStr Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis
title_full_unstemmed Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis
title_short Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis
title_sort involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367233/
https://www.ncbi.nlm.nih.gov/pubmed/36157548
http://dx.doi.org/10.3748/wjg.v28.i29.3854
work_keys_str_mv AT liyanrong involvementofnitrergicneuronsincolonicmotilityinaratmodelofulcerativecolitis
AT liyan involvementofnitrergicneuronsincolonicmotilityinaratmodelofulcerativecolitis
AT jinyuan involvementofnitrergicneuronsincolonicmotilityinaratmodelofulcerativecolitis
AT xumang involvementofnitrergicneuronsincolonicmotilityinaratmodelofulcerativecolitis
AT fanhongwei involvementofnitrergicneuronsincolonicmotilityinaratmodelofulcerativecolitis
AT zhangqian involvementofnitrergicneuronsincolonicmotilityinaratmodelofulcerativecolitis
AT tanguohe involvementofnitrergicneuronsincolonicmotilityinaratmodelofulcerativecolitis
AT chenjing involvementofnitrergicneuronsincolonicmotilityinaratmodelofulcerativecolitis
AT liyunqing involvementofnitrergicneuronsincolonicmotilityinaratmodelofulcerativecolitis