Cargando…
Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized primarily at the apical or luminal surfaces of epithelial cells that line the airway, gut, and exocrine glands; it is well established that CFTR plays a pivotal role in cholera toxin (CTX)-i...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2005
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213164/ https://www.ncbi.nlm.nih.gov/pubmed/16203867 http://dx.doi.org/10.1084/jem.20050421 |
_version_ | 1782148838908231680 |
---|---|
author | Li, Chunying Dandridge, Keanna S. Di, Anke Marrs, Kevin L. Harris, Erica L. Roy, Koushik Jackson, John S. Makarova, Natalia V. Fujiwara, Yuko Farrar, Patricia L. Nelson, Deborah J. Tigyi, Gabor J. Naren, Anjaparavanda P. |
author_facet | Li, Chunying Dandridge, Keanna S. Di, Anke Marrs, Kevin L. Harris, Erica L. Roy, Koushik Jackson, John S. Makarova, Natalia V. Fujiwara, Yuko Farrar, Patricia L. Nelson, Deborah J. Tigyi, Gabor J. Naren, Anjaparavanda P. |
author_sort | Li, Chunying |
collection | PubMed |
description | The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized primarily at the apical or luminal surfaces of epithelial cells that line the airway, gut, and exocrine glands; it is well established that CFTR plays a pivotal role in cholera toxin (CTX)-induced secretory diarrhea. Lysophosphatidic acid (LPA), a naturally occurring phospholipid present in blood and foods, has been reported to play a vital role in a variety of conditions involving gastrointestinal wound repair, apoptosis, inflammatory bowel disease, and diarrhea. Here we show, for the first time, that type 2 LPA receptors (LPA(2)) are expressed at the apical surface of intestinal epithelial cells, where they form a macromolecular complex with Na(+)/H(+) exchanger regulatory factor–2 and CFTR through a PSD95/Dlg/ZO-1–based interaction. LPA inhibited CFTR-dependent iodide efflux through LPA(2)-mediated G(i) pathway, and LPA inhibited CFTR-mediated short-circuit currents in a compartmentalized fashion. CFTR-dependent intestinal fluid secretion induced by CTX in mice was reduced substantially by LPA administration; disruption of this complex using a cell-permeant LPA(2)-specific peptide reversed LPA(2)-mediated inhibition. Thus, LPA-rich foods may represent an alternative method of treating certain forms of diarrhea. |
format | Text |
id | pubmed-2213164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22131642008-03-11 Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions Li, Chunying Dandridge, Keanna S. Di, Anke Marrs, Kevin L. Harris, Erica L. Roy, Koushik Jackson, John S. Makarova, Natalia V. Fujiwara, Yuko Farrar, Patricia L. Nelson, Deborah J. Tigyi, Gabor J. Naren, Anjaparavanda P. J Exp Med Article The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized primarily at the apical or luminal surfaces of epithelial cells that line the airway, gut, and exocrine glands; it is well established that CFTR plays a pivotal role in cholera toxin (CTX)-induced secretory diarrhea. Lysophosphatidic acid (LPA), a naturally occurring phospholipid present in blood and foods, has been reported to play a vital role in a variety of conditions involving gastrointestinal wound repair, apoptosis, inflammatory bowel disease, and diarrhea. Here we show, for the first time, that type 2 LPA receptors (LPA(2)) are expressed at the apical surface of intestinal epithelial cells, where they form a macromolecular complex with Na(+)/H(+) exchanger regulatory factor–2 and CFTR through a PSD95/Dlg/ZO-1–based interaction. LPA inhibited CFTR-dependent iodide efflux through LPA(2)-mediated G(i) pathway, and LPA inhibited CFTR-mediated short-circuit currents in a compartmentalized fashion. CFTR-dependent intestinal fluid secretion induced by CTX in mice was reduced substantially by LPA administration; disruption of this complex using a cell-permeant LPA(2)-specific peptide reversed LPA(2)-mediated inhibition. Thus, LPA-rich foods may represent an alternative method of treating certain forms of diarrhea. The Rockefeller University Press 2005-10-03 /pmc/articles/PMC2213164/ /pubmed/16203867 http://dx.doi.org/10.1084/jem.20050421 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Li, Chunying Dandridge, Keanna S. Di, Anke Marrs, Kevin L. Harris, Erica L. Roy, Koushik Jackson, John S. Makarova, Natalia V. Fujiwara, Yuko Farrar, Patricia L. Nelson, Deborah J. Tigyi, Gabor J. Naren, Anjaparavanda P. Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions |
title | Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions |
title_full | Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions |
title_fullStr | Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions |
title_full_unstemmed | Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions |
title_short | Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions |
title_sort | lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through cftr-dependent protein interactions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213164/ https://www.ncbi.nlm.nih.gov/pubmed/16203867 http://dx.doi.org/10.1084/jem.20050421 |
work_keys_str_mv | AT lichunying lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT dandridgekeannas lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT dianke lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT marrskevinl lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT harriserical lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT roykoushik lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT jacksonjohns lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT makarovanataliav lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT fujiwarayuko lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT farrarpatricial lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT nelsondeborahj lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT tigyigaborj lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions AT narenanjaparavandap lysophosphatidicacidinhibitscholeratoxininducedsecretorydiarrheathroughcftrdependentproteininteractions |