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Novel aspects of cholinergic regulation of colonic ion transport
Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiment...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492755/ https://www.ncbi.nlm.nih.gov/pubmed/26236483 http://dx.doi.org/10.1002/prp2.139 |
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author | Bader, Sandra Diener, Martin |
author_facet | Bader, Sandra Diener, Martin |
author_sort | Bader, Sandra |
collection | PubMed |
description | Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (I(sc)) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I(sc) was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M(1) and M(3) receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M(3) receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport – up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors – is more complex than previously assumed. |
format | Online Article Text |
id | pubmed-4492755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-44927552015-07-31 Novel aspects of cholinergic regulation of colonic ion transport Bader, Sandra Diener, Martin Pharmacol Res Perspect Original Articles Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (I(sc)) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I(sc) was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M(1) and M(3) receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M(3) receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport – up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors – is more complex than previously assumed. John Wiley & Sons, Ltd 2015-06 2015-05-04 /pmc/articles/PMC4492755/ /pubmed/26236483 http://dx.doi.org/10.1002/prp2.139 Text en © 2015 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Bader, Sandra Diener, Martin Novel aspects of cholinergic regulation of colonic ion transport |
title | Novel aspects of cholinergic regulation of colonic ion transport |
title_full | Novel aspects of cholinergic regulation of colonic ion transport |
title_fullStr | Novel aspects of cholinergic regulation of colonic ion transport |
title_full_unstemmed | Novel aspects of cholinergic regulation of colonic ion transport |
title_short | Novel aspects of cholinergic regulation of colonic ion transport |
title_sort | novel aspects of cholinergic regulation of colonic ion transport |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492755/ https://www.ncbi.nlm.nih.gov/pubmed/26236483 http://dx.doi.org/10.1002/prp2.139 |
work_keys_str_mv | AT badersandra novelaspectsofcholinergicregulationofcoloniciontransport AT dienermartin novelaspectsofcholinergicregulationofcoloniciontransport |