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Age‐related differences of γ‐aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle
BACKGROUND: Enteric neurons undergo to functional changes during aging. We investigated the possible age‐associated differences in enteric γ‐aminobutyric acid (GABA)ergic transmission evaluating function and distribution of GABAergic receptors in human colon. METHODS: Mechanical responses to GABA an...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285353/ https://www.ncbi.nlm.nih.gov/pubmed/34432349 http://dx.doi.org/10.1111/nmo.14248 |
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author | Zizzo, Maria Grazia Cicio, Adele Raimondo, Stefania Alessandro, Riccardo Serio, Rosa |
author_facet | Zizzo, Maria Grazia Cicio, Adele Raimondo, Stefania Alessandro, Riccardo Serio, Rosa |
author_sort | Zizzo, Maria Grazia |
collection | PubMed |
description | BACKGROUND: Enteric neurons undergo to functional changes during aging. We investigated the possible age‐associated differences in enteric γ‐aminobutyric acid (GABA)ergic transmission evaluating function and distribution of GABAergic receptors in human colon. METHODS: Mechanical responses to GABA and GABA receptor agonists on slow phasic contractions were examined in vitro as changes in isometric tension in colonic muscle strips from young (<65 years old) and aged patients (>65 years old). GABAergic receptor expression was assessed by quantitative RT‐PCR. KEY RESULTS: In both preparations GABA induced an excitatory effect, consisting in an increase in the basal tone, antagonized by the GABAA receptor antagonist, bicuculline, and potentiated by phaclofen, GABAB receptor antagonist.Tetrodotoxin (TTX) and atropine‐sensitive contractile responses to GABA and GABAA receptor agonist, muscimol, were more pronounced in old compared to young subjects. Baclofen, GABAB receptor agonist, induced a TTX‐sensitive reduction of the amplitude of the spontaneous. Nω–nitro‐l‐arginine methyl ester (L‐NAME), nitric oxide (NO) synthase inhibitor abolished the inhibitory responses in old preparations, but a residual responses persisted in young preparations, which in turn was abolished by suramin, purinergic receptor antagonist. α3–GABAA receptor subunit expression tends to change in an age‐dependent manner. CONCLUSIONS AND INFERENCES: Our results reveal age‐related differences in GABAergic transmission in human colon. At all the age tested GABA regulates muscular contractility modulating the activity of the intrinsic neurons. Activation of GABAA receptor, through acetylcholine release, induces contraction, which increases in amplitude with age. GABAB receptor activation leads to neural release of NO and purines, being a loss of purinergic‐component in aged group. |
format | Online Article Text |
id | pubmed-9285353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92853532022-07-15 Age‐related differences of γ‐aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle Zizzo, Maria Grazia Cicio, Adele Raimondo, Stefania Alessandro, Riccardo Serio, Rosa Neurogastroenterol Motil Original Articles BACKGROUND: Enteric neurons undergo to functional changes during aging. We investigated the possible age‐associated differences in enteric γ‐aminobutyric acid (GABA)ergic transmission evaluating function and distribution of GABAergic receptors in human colon. METHODS: Mechanical responses to GABA and GABA receptor agonists on slow phasic contractions were examined in vitro as changes in isometric tension in colonic muscle strips from young (<65 years old) and aged patients (>65 years old). GABAergic receptor expression was assessed by quantitative RT‐PCR. KEY RESULTS: In both preparations GABA induced an excitatory effect, consisting in an increase in the basal tone, antagonized by the GABAA receptor antagonist, bicuculline, and potentiated by phaclofen, GABAB receptor antagonist.Tetrodotoxin (TTX) and atropine‐sensitive contractile responses to GABA and GABAA receptor agonist, muscimol, were more pronounced in old compared to young subjects. Baclofen, GABAB receptor agonist, induced a TTX‐sensitive reduction of the amplitude of the spontaneous. Nω–nitro‐l‐arginine methyl ester (L‐NAME), nitric oxide (NO) synthase inhibitor abolished the inhibitory responses in old preparations, but a residual responses persisted in young preparations, which in turn was abolished by suramin, purinergic receptor antagonist. α3–GABAA receptor subunit expression tends to change in an age‐dependent manner. CONCLUSIONS AND INFERENCES: Our results reveal age‐related differences in GABAergic transmission in human colon. At all the age tested GABA regulates muscular contractility modulating the activity of the intrinsic neurons. Activation of GABAA receptor, through acetylcholine release, induces contraction, which increases in amplitude with age. GABAB receptor activation leads to neural release of NO and purines, being a loss of purinergic‐component in aged group. John Wiley and Sons Inc. 2021-08-25 2022-03 /pmc/articles/PMC9285353/ /pubmed/34432349 http://dx.doi.org/10.1111/nmo.14248 Text en © 2021 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Zizzo, Maria Grazia Cicio, Adele Raimondo, Stefania Alessandro, Riccardo Serio, Rosa Age‐related differences of γ‐aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle |
title | Age‐related differences of γ‐aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle |
title_full | Age‐related differences of γ‐aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle |
title_fullStr | Age‐related differences of γ‐aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle |
title_full_unstemmed | Age‐related differences of γ‐aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle |
title_short | Age‐related differences of γ‐aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle |
title_sort | age‐related differences of γ‐aminobutyric acid (gaba)ergic transmission in human colonic smooth muscle |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285353/ https://www.ncbi.nlm.nih.gov/pubmed/34432349 http://dx.doi.org/10.1111/nmo.14248 |
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