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Epinephrine modulates Na(+)/K(+) ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2
Epinephrine, a key stress hormone, is known to affect ion transport in the colon. Stress has been associated with alterations in colonic functions leading to changes in water movements manifested as diarrhea or constipation. Colonic water movement is driven by the Na(+)-gradient created by the Na(+)...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821373/ https://www.ncbi.nlm.nih.gov/pubmed/29466417 http://dx.doi.org/10.1371/journal.pone.0193139 |
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author | El Moussawi, Layla Chakkour, Mohamed Kreydiyyeh, Sawsan I. |
author_facet | El Moussawi, Layla Chakkour, Mohamed Kreydiyyeh, Sawsan I. |
author_sort | El Moussawi, Layla |
collection | PubMed |
description | Epinephrine, a key stress hormone, is known to affect ion transport in the colon. Stress has been associated with alterations in colonic functions leading to changes in water movements manifested as diarrhea or constipation. Colonic water movement is driven by the Na(+)-gradient created by the Na(+)/K(+)-ATPase. Whether epinephrine acts via an effect on the Na(+)/K(+)-ATPase hasn’t been studied before. The aim of this work was to investigate the effect of epinephrine on the Na(+)/K(+)-ATPase and to elucidate the signaling pathway involved using CaCo-2 cells as a model. The activity of the Na(+)/K(+)-ATPase was assayed by measuring the amount of inorganic phosphate released in presence and absence of ouabain, a specific inhibitor of the enzyme. Epinephrine, added for 20 minutes, decreased the activity of the Na(+)/K(+)-ATPase by around 50%. This effect was found to be mediated by α2 adrenergic receptors as it was fully abolished in the presence of yohimbine an α2-blocker, but persisted in presence of other adrenergic antagonists. Furthermore, treatment with Rp-cAMP, a PKA inhibitor, mimicked epinephrine’s negative effect and didn’t result in any additional inhibition when both were added simultaneously. Treatment with indomethacin, PP2, SB202190, and PD98059, respective inhibitors of COX enzymes, Src, p38MAPK, and ERK completely abrogated the effect of epinephrine. The effect of epinephrine did not appear also in presence of inhibitors of all four different types of PGE2 receptors. Western blot analysis revealed an epinephrine-induced increase in the phosphorylation of p38 MAPK and ERK that disappeared in presence of respectively PP2 and SB2020190. In addition, an inhibitory effect, similar to that of epinephrine’s, was observed upon incubation with PGE2. It was concluded that epinephrine inhibits the Na(+)/K(+)-ATPase by the sequential activation of α2 adrenergic receptors, Src, p38MAPK, and ERK leading to PGE2 release. |
format | Online Article Text |
id | pubmed-5821373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58213732018-03-02 Epinephrine modulates Na(+)/K(+) ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2 El Moussawi, Layla Chakkour, Mohamed Kreydiyyeh, Sawsan I. PLoS One Research Article Epinephrine, a key stress hormone, is known to affect ion transport in the colon. Stress has been associated with alterations in colonic functions leading to changes in water movements manifested as diarrhea or constipation. Colonic water movement is driven by the Na(+)-gradient created by the Na(+)/K(+)-ATPase. Whether epinephrine acts via an effect on the Na(+)/K(+)-ATPase hasn’t been studied before. The aim of this work was to investigate the effect of epinephrine on the Na(+)/K(+)-ATPase and to elucidate the signaling pathway involved using CaCo-2 cells as a model. The activity of the Na(+)/K(+)-ATPase was assayed by measuring the amount of inorganic phosphate released in presence and absence of ouabain, a specific inhibitor of the enzyme. Epinephrine, added for 20 minutes, decreased the activity of the Na(+)/K(+)-ATPase by around 50%. This effect was found to be mediated by α2 adrenergic receptors as it was fully abolished in the presence of yohimbine an α2-blocker, but persisted in presence of other adrenergic antagonists. Furthermore, treatment with Rp-cAMP, a PKA inhibitor, mimicked epinephrine’s negative effect and didn’t result in any additional inhibition when both were added simultaneously. Treatment with indomethacin, PP2, SB202190, and PD98059, respective inhibitors of COX enzymes, Src, p38MAPK, and ERK completely abrogated the effect of epinephrine. The effect of epinephrine did not appear also in presence of inhibitors of all four different types of PGE2 receptors. Western blot analysis revealed an epinephrine-induced increase in the phosphorylation of p38 MAPK and ERK that disappeared in presence of respectively PP2 and SB2020190. In addition, an inhibitory effect, similar to that of epinephrine’s, was observed upon incubation with PGE2. It was concluded that epinephrine inhibits the Na(+)/K(+)-ATPase by the sequential activation of α2 adrenergic receptors, Src, p38MAPK, and ERK leading to PGE2 release. Public Library of Science 2018-02-21 /pmc/articles/PMC5821373/ /pubmed/29466417 http://dx.doi.org/10.1371/journal.pone.0193139 Text en © 2018 El Moussawi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article El Moussawi, Layla Chakkour, Mohamed Kreydiyyeh, Sawsan I. Epinephrine modulates Na(+)/K(+) ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2 |
title | Epinephrine modulates Na(+)/K(+) ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2 |
title_full | Epinephrine modulates Na(+)/K(+) ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2 |
title_fullStr | Epinephrine modulates Na(+)/K(+) ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2 |
title_full_unstemmed | Epinephrine modulates Na(+)/K(+) ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2 |
title_short | Epinephrine modulates Na(+)/K(+) ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2 |
title_sort | epinephrine modulates na(+)/k(+) atpase activity in caco-2 cells via src, p38mapk, erk and pge2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821373/ https://www.ncbi.nlm.nih.gov/pubmed/29466417 http://dx.doi.org/10.1371/journal.pone.0193139 |
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