Hyperpermeability of intestinal epithelial monolayers is induced by NO: effect of low extracellular pH

The American Journal of Physiology
N UnnoM P Fink

Abstract

Nitric oxide (NO.) increases the permeability of Caco-2BBe enterocytic monolayers. Many of the toxic effects of NO. are thought to be mediated by the peroxynitrite anion (ONOO-), which, under mildly acidic conditions, can rearrange to yield an intermediate with reactivity similar to toxic OH.. Accordingly, we assessed the permeability of Caco-2BBe cells grown on permeable supports for 24 h in media titrated to normal or acidic extracellular pH (pHo) with or without the NO. donors 3-morpholinosydnonimine (SIN-1) or sodium nitroprusside (SNP). Incubation with 2 mM SIN-1 at pHo 6.8 or 0.6 mM SNP at pHo 6.5 increased permeability (apical-to-basolateral flux of fluorescein sulfonic acid), whereas at pHo 7.4 permeability was unaffected by these concentrations of NO. donors. Accumulation of NO2/NO3 in medium (index of NO. release) was not increased by incubation of cells with SIN-1 or SNP under mildly acidic conditions. Under acidic but not control conditions, incubation with SIN-1 caused disruption of perijunctional actin filaments as assessed by fluorescence microscopy. At pHo 6.8 and 6.5 (but not 7.4), SIN-1 significantly decreased intracellular levels of both ATP and glutathione. Incubation with 5 mM deferoxamine or 500 uM ascorbi...Continue Reading

Citations

Apr 19, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·A BananA Keshavarzian
Mar 11, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jan-Michel Otte, Daniel K Podolsky
Oct 23, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hiroshi HommaEdwin A Deitch
Apr 12, 2019·International Journal of Molecular Sciences·Kaiwen MuDavid D Kitts
May 4, 2000·American Journal of Physiology. Cell Physiology·G I Gorodeski
Feb 7, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Cécile BeaurepaireDerek M McKay
Aug 27, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jody L GookinMichael P Murtaugh
Aug 24, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·A BananA Keshavarzian
May 25, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jody L GookinRobert A Argenzio
Sep 12, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·A BananA Keshavarzian
Feb 13, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·S R KleebergerA E Jedlicka

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