Mechanisms of lysophosphatidic acid (LPA) mediated stimulation of intestinal apical Cl-/OH- exchange

Amika Singla, Alka Dwivedi, Seema Saksena, Ravinder K. Gill, Waddah A. Alrefai, Krishnamurthy Ramaswamy, Pradeep K. Dudeja

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Lysophosphatidic acid (LPA), a potent bioactive phospholipid, is a natural component of food products like soy and egg yolk. LPA modulates a number of epithelial functions and has been shown to inhibit cholera toxin-induced diarrhea. Antidiarrheal effects of LPA are known to be mediated by inhibiting chloride secretion. However, the effects of LPA on chloride absorption in the mammalian intestine are not known. The present studies examined the effects of LPA on apical Cl-/OH- exchangers known to be involved in chloride absorption in intestinal epithelial cells. Caco-2 cells were treated with LPA, and Cl-/OH- exchange activity was measured as DIDS-sensitive 36Cl- uptake. Cell surface biotinylation studies were performed to evaluate the effect of LPA on cell surface levels of apical Cl -/OH- exchangers, downregulated in adenoma (DRA) (SLC26A3), and putative anion transporter-1 (SLC26A6). Treatment of Caco-2 cells with LPA (100 μM) significantly stimulated Cl-/OH- exchange activity. Specific agonist for LPA2 receptor mimicked the effects of LPA. LPA-mediated stimulation of Cl-/OH- exchange activity was dependent on activation of phosphatidylinositol 3-kinase/Akt signaling pathway. Consistent with the functional activity, LPA treatment resulted in increased levels of DRA on the apical membrane. Our results demonstrate that LPA stimulates apical Cl-/OH- exchange activity and surface levels of DRA in intestinal epithelial cells. This increase in Cl-/OH- exchange may contribute to the antidiarrheal effects of LPA.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume298
Issue number2
DOIs
StatePublished - Feb 1 2010

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Adenoma
Antidiarrheals
Chlorides
Caco-2 Cells
Down-Regulation
hydroxide ion
lysophosphatidic acid
Epithelial Cells
Lysophosphatidic Acid Receptors
Phosphatidylinositol 3-Kinase
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Biotinylation
Egg Yolk
Cholera Toxin
Intestinal Absorption
Intestines
Anions
Diarrhea
Phospholipids
Food

Keywords

  • Chloride absorption
  • Downregulated in adenoma
  • Human intestine
  • LPA receptor 2
  • Phosphatidylinositol 3-kinase/Akt

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Mechanisms of lysophosphatidic acid (LPA) mediated stimulation of intestinal apical Cl-/OH- exchange. / Singla, Amika; Dwivedi, Alka; Saksena, Seema; Gill, Ravinder K.; Alrefai, Waddah A.; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 298, No. 2, 01.02.2010.

Research output: Contribution to journalArticle

Singla, Amika ; Dwivedi, Alka ; Saksena, Seema ; Gill, Ravinder K. ; Alrefai, Waddah A. ; Ramaswamy, Krishnamurthy ; Dudeja, Pradeep K. / Mechanisms of lysophosphatidic acid (LPA) mediated stimulation of intestinal apical Cl-/OH- exchange. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2010 ; Vol. 298, No. 2.
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AB - Lysophosphatidic acid (LPA), a potent bioactive phospholipid, is a natural component of food products like soy and egg yolk. LPA modulates a number of epithelial functions and has been shown to inhibit cholera toxin-induced diarrhea. Antidiarrheal effects of LPA are known to be mediated by inhibiting chloride secretion. However, the effects of LPA on chloride absorption in the mammalian intestine are not known. The present studies examined the effects of LPA on apical Cl-/OH- exchangers known to be involved in chloride absorption in intestinal epithelial cells. Caco-2 cells were treated with LPA, and Cl-/OH- exchange activity was measured as DIDS-sensitive 36Cl- uptake. Cell surface biotinylation studies were performed to evaluate the effect of LPA on cell surface levels of apical Cl -/OH- exchangers, downregulated in adenoma (DRA) (SLC26A3), and putative anion transporter-1 (SLC26A6). Treatment of Caco-2 cells with LPA (100 μM) significantly stimulated Cl-/OH- exchange activity. Specific agonist for LPA2 receptor mimicked the effects of LPA. LPA-mediated stimulation of Cl-/OH- exchange activity was dependent on activation of phosphatidylinositol 3-kinase/Akt signaling pathway. Consistent with the functional activity, LPA treatment resulted in increased levels of DRA on the apical membrane. Our results demonstrate that LPA stimulates apical Cl-/OH- exchange activity and surface levels of DRA in intestinal epithelial cells. This increase in Cl-/OH- exchange may contribute to the antidiarrheal effects of LPA.

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