Cargando…

Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity

The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. The present study was designed to investigate roles of adrenergic signaling and the endogenous hydrogen sulfide producing enzyme cystathionine β-synthetase (CBS) in a previously validated...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Liyan, Zhao, Liting, Qu, Ruobing, Zhu, Hong-Yan, Wang, Yongmeng, Jiang, Xinghong, Xu, Guang-Yin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630780/
https://www.ncbi.nlm.nih.gov/pubmed/26527188
http://dx.doi.org/10.1038/srep16109
_version_ 1782398770534678528
author Zhu, Liyan
Zhao, Liting
Qu, Ruobing
Zhu, Hong-Yan
Wang, Yongmeng
Jiang, Xinghong
Xu, Guang-Yin
author_facet Zhu, Liyan
Zhao, Liting
Qu, Ruobing
Zhu, Hong-Yan
Wang, Yongmeng
Jiang, Xinghong
Xu, Guang-Yin
author_sort Zhu, Liyan
collection PubMed
description The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. The present study was designed to investigate roles of adrenergic signaling and the endogenous hydrogen sulfide producing enzyme cystathionine β-synthetase (CBS) in a previously validated rat model of IBS induced by neonatal colonic inflammation (NCI). Here we showed that NCI-induced visceral hypersensitivity (VH) was significantly attenuated by β(2) subunit inhibitor but not by β(1) or β(3) or α subunit inhibitor. NCI markedly elevated plasma norepinephrine (NE) concentration without alteration in expression of β(2) subunit receptors in dorsal root ganglion (DRGs) innervating the colon. In addition, NCI markedly enhanced TRPV1 and CBS expression in the colon DRGs. CBS inhibitor AOAA reversed the upregulation of TRPV1 in NCI rats. In vitro experiments showed that incubation of DRG cells with NE markedly enhanced expression of TRPV1, which was reversed by application of AOAA. Incubation of DRG cells with the H(2)S donor NaHS greatly enhanced TRPV1 expression. Collectively, these data suggest that activation of adrenergic signaling by NCI sensitizes TRPV1 channel activity, which is likely mediated by upregulation of CBS expression in peripheral sensory neurons, thus contributing to chronic visceral hypersensitivity.
format Online
Article
Text
id pubmed-4630780
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-46307802015-11-16 Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity Zhu, Liyan Zhao, Liting Qu, Ruobing Zhu, Hong-Yan Wang, Yongmeng Jiang, Xinghong Xu, Guang-Yin Sci Rep Article The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. The present study was designed to investigate roles of adrenergic signaling and the endogenous hydrogen sulfide producing enzyme cystathionine β-synthetase (CBS) in a previously validated rat model of IBS induced by neonatal colonic inflammation (NCI). Here we showed that NCI-induced visceral hypersensitivity (VH) was significantly attenuated by β(2) subunit inhibitor but not by β(1) or β(3) or α subunit inhibitor. NCI markedly elevated plasma norepinephrine (NE) concentration without alteration in expression of β(2) subunit receptors in dorsal root ganglion (DRGs) innervating the colon. In addition, NCI markedly enhanced TRPV1 and CBS expression in the colon DRGs. CBS inhibitor AOAA reversed the upregulation of TRPV1 in NCI rats. In vitro experiments showed that incubation of DRG cells with NE markedly enhanced expression of TRPV1, which was reversed by application of AOAA. Incubation of DRG cells with the H(2)S donor NaHS greatly enhanced TRPV1 expression. Collectively, these data suggest that activation of adrenergic signaling by NCI sensitizes TRPV1 channel activity, which is likely mediated by upregulation of CBS expression in peripheral sensory neurons, thus contributing to chronic visceral hypersensitivity. Nature Publishing Group 2015-11-03 /pmc/articles/PMC4630780/ /pubmed/26527188 http://dx.doi.org/10.1038/srep16109 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhu, Liyan
Zhao, Liting
Qu, Ruobing
Zhu, Hong-Yan
Wang, Yongmeng
Jiang, Xinghong
Xu, Guang-Yin
Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity
title Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity
title_full Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity
title_fullStr Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity
title_full_unstemmed Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity
title_short Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity
title_sort adrenergic stimulation sensitizes trpv1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630780/
https://www.ncbi.nlm.nih.gov/pubmed/26527188
http://dx.doi.org/10.1038/srep16109
work_keys_str_mv AT zhuliyan adrenergicstimulationsensitizestrpv1throughupregulationofcystathioninebsynthetaseinaratmodelofvisceralhypersensitivity
AT zhaoliting adrenergicstimulationsensitizestrpv1throughupregulationofcystathioninebsynthetaseinaratmodelofvisceralhypersensitivity
AT quruobing adrenergicstimulationsensitizestrpv1throughupregulationofcystathioninebsynthetaseinaratmodelofvisceralhypersensitivity
AT zhuhongyan adrenergicstimulationsensitizestrpv1throughupregulationofcystathioninebsynthetaseinaratmodelofvisceralhypersensitivity
AT wangyongmeng adrenergicstimulationsensitizestrpv1throughupregulationofcystathioninebsynthetaseinaratmodelofvisceralhypersensitivity
AT jiangxinghong adrenergicstimulationsensitizestrpv1throughupregulationofcystathioninebsynthetaseinaratmodelofvisceralhypersensitivity
AT xuguangyin adrenergicstimulationsensitizestrpv1throughupregulationofcystathioninebsynthetaseinaratmodelofvisceralhypersensitivity