Ammonia inhibits cAMP-regulated intestinal Cl- transport. Asymmetric effects of apical and basolateral exposure and implications for epithelial barrier function.

Prasad, Madhu; Smith, Jeremy A.; Resnick, Andrew; Awtrey, Christopher S.; Hrnjez, Bruce J.; Matthews, Jeffrey B.

doi:10.1172/jci118268

Cited by 30 publications

(17 citation statements)

References 46 publications

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“…It has been shown that CDCA and DCA but not CA induce colonic chloride secretion [7,13], and ammonia inhibits chloride secretion by human intestinal epithelial cells [18]. The present study has demonstrated that not only CDCA and DCA but also CA and ammonium chloride enhanced neutrophil adhesion to intestinal epithelial HT29 cells, suggesting that the mechanism of bile acid-and ammonia-induced …”

Section: Discussionsupporting

confidence: 55%

“…These agents are chronically exposed to colonic epithelial cells, and can modulate the intestinal functions [12,17]. In fact, it has been reported that bile acids and ammonia influence intestinal epithelial functions such as secretion of electrolytes and water [7,[12][13][14]18]. Moreover, it has been shown by in vivo studies that injection of CDCA and DCA in the colon, and perfusion with ammonium chloride induces neutrophil accumulation in the lamina propria [7,19].…”

Section: Discussionmentioning

confidence: 99%

“…However, little has been known about the effect of ammonia on intestinal mucosal functions. Recently, it has been reported that ammonia inhibits cyclic nucleotide (cAMP and cGMP)-mediated chloride (Cl -) secretion by T84 human intestinal epithelial cells [18]. Moreover, it has been shown that perfusion of rats with ammonium chloride induce neutrophil infiltration in the colon [19].…”

Section: Introductionmentioning

confidence: 99%

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Exposure of intestinal epithelial cell HT29 to bile acids and ammonia enhances Mac-1-mediated neutrophil adhesion

et al. 1999

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These observations indicate that exposure of HT29 cells to bile acids or ammonia induces CD11b/CD18 (Mac-1) dependent- but CD11a/CD18 (LFA-1) independent-neutrophil adhesion to intestinal epithelial cells, and ICAM-1 is unlikely involved in the interactions. Furthermore, epithelial ligand(s) for neutrophils are protein molecule(s) which are expressed on the cell surface independent of protein synthesis.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exposure of intestinal epithelial cell HT29 to bile acids and ammonia enhances Mac-1-mediated neutrophil adhesion

et al. 1999

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“…None of our patients experienced bleeding or developed petechiae, although we were careful to exclude patients with a history of airway or gastrointestinal bleeding. It is also possible that GSNO metabolites such as NO and NH 4 ϩ could have adverse effects on the CF airway (29, 39-41), though measured NO and predicted NH 4 ϩ (low M) concentrations were log orders below those shown to be physiologically or pathologically relevant (39,41,42).…”

Section: Discussionmentioning

confidence: 99%

Acute Effects of Aerosolized S-Nitrosoglutathione in Cystic Fibrosis

Snyder

McPherson

Hunt

et al. 2002

Am J Respir Crit Care Med

122

110

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S -Nitrosoglutathione (GSNO), a naturally occurring constituent of airway lining fluid, enhances ciliary motility, relaxes airway smooth muscle, inhibits airway epithelial amiloride-sensitive sodium transport, and prevents pathogen replication. Remarkably, airway levels of GSNO are low in patients with cystic fibrosis (CF). We hypothesized that replacement of airway GSNO would improve gas exchange in CF. In a double-blind, placebo controlled study, we administered 0.05 ml/kg of 10 mM GSNO or phosphate buffered saline by aerosol to patients with CF and followed oxygen saturation, spirometry, respiratory rate, blood pressure, heart rate, and expired nitric oxide (NO). Nine patients received GSNO and 11 placebo. GSNO inhalation was associated with a modest but sustained increase in oxygen saturation at all time points. Expired NO increased in the low ppb range with GSNO treatment, peaking at 5 minutes but remaining above baseline at 30 minutes. There were no adverse effects. We conclude that GSNO is well tolerated in patients with CF and improves oxygenation through a mechanism that may be independent of free NO. Further, GSNO breakdown increases expired NO. We suggest that therapy aimed at restoring endogenous GSNO levels in the CF airway may merit study.

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“…Taken together, our results clearly suggest inhibition of basolateral K ‡ conductance as major mechanism of the antisecretory action of loperamide. In fact, inhibition of basolateral K ‡ conductance is increasingly recognized as an important target of agents inhibiting intestinal Cl ¡ secretion (20,21,27,29,30). Interestingly, this heterogeneous group of biochemically unrelated agents (including ammonia, cromanol derivatives, clotrimazole, levamisole and somatostatin) is not characterized by any obvious structural similarities.…”

Section: Inhibition Of Basolateral K ‡ Conductancementioning

confidence: 99%

Antisecretory Effect of Loperamide in Colon Epithelial Cells by Inhibition of Basolateral K+ Conductance

Epple

Fromm²,

Riecken³

et al. 2001

Scandinavian Journal of Gastroenterology

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Loperamide (5 x 10(-5) M) inhibited I(SC) stimulated by FSK, CCh and PMA. The antisecretory action of loperamide was unaffected by preincubation with naloxone (10(-5) M). Furthermore, loperamide strongly inhibited basolateral 86Rb efflux. Like loperamide, the calmodulin antagonist trifluoperazine (10(-4) M) inhibited I(SC) induced by FSK, CCh or PMA. The Ca2+ channel blocker verapamil (5 x 10(-5) M), on the other hand, inhibited only PMA-stimulated I(SC),but had no effect on FSK or CCh-induced I(SC) CONCLUSIONS: Loperamide exerts a direct antisecretory action on chloride secretion of colon epithelial cells independently of the respective stimulatory signal transduction pathway. This antisecretory effect is not mediated by opiate receptors and reflects inhibition of basolateral K+ conductance.

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Ammonia inhibits cAMP-regulated intestinal Cl- transport. Asymmetric effects of apical and basolateral exposure and implications for epithelial barrier function.

Cited by 30 publications

References 46 publications

Exposure of intestinal epithelial cell HT29 to bile acids and ammonia enhances Mac-1-mediated neutrophil adhesion

Exposure of intestinal epithelial cell HT29 to bile acids and ammonia enhances Mac-1-mediated neutrophil adhesion

Acute Effects of Aerosolized S-Nitrosoglutathione in Cystic Fibrosis

Antisecretory Effect of Loperamide in Colon Epithelial Cells by Inhibition of Basolateral K+ Conductance

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