Effects of aspirin and acetic acid on intracellular pH in necturus gastric mucosa

Ashley, Stanley W.; Soybel, David I.; Moore, Carolyn; Cheung, Laurence Y.

doi:10.1016/0002-9610(89)90421-2

Cited by 6 publications

(2 citation statements)

References 18 publications

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“…The pH of freshly secreted gastric mucus has never been measured directly but is believed to reflect the intracellular pH of the mucus-secreting cells (Ϸ7) (15). It is known that gastric epithelial cells are sensitive to acidifications coming from the blood side (22). To decrease the intracellular pH in the mucus producing cells, the arterial pH was lowered to Ϸ7.15 through the increase of the inspiratory fraction of CO 2 to 8%.…”

Section: Resultsmentioning

confidence: 99%

The spatial orientation of Helicobacter pylori in the gastric mucus

Schreiber

Konradt

Groll

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

288

261

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The highly motile human pathogen Helicobacter pylori lives deep in the gastric mucus layer. To identify which chemical gradient guides the bacteria within the mucus layer, combinations of luminal perfusion, dialysis, and ventilation were used to modify or invert transmucus gradients in anaesthetized Helicobacterinfected mice and Mongolian gerbils. Neither changes in lumen or arterial pH nor inversion of bicarbonate͞CO2 or urea͞ammonium gradients disturbed Helicobacter orientation. However, elimination of the mucus pH gradient by simultaneous reduction of arterial pH and bicarbonate concentration perturbed orientation, causing the bacteria to spread over the entire mucus layer. H. pylori thus uses the gastric mucus pH gradient for chemotactic orientation. Helicobacter pylori, a motile Gram-negative human pathogen that causes gastritis and duodenal and gastric ulcers and increases the risk of gastric cancer (1), lives within the gastric mucus layer. The majority of bacteria are located deep in the mucus, close to the surface of the epithelium. The mucus is continuously secreted in the glands and by surface epithelial cells and is degraded at the luminal surface (2). Because of this rapid mucus turnover, the bacteria need motility and spatial orientation to avoid being carried into the lumen, where the acidic pH inhibits growth and paralyzes motility (3, 4). Orientation therefore plays a central role in acute colonization and the chronic persistence of H. pylori.Motile bacteria sense chemical gradients by means of chemoreceptor proteins and relay the information to the flagellar motor (5). In the case of H. pylori, it must be a chemical gradient in the gastric mucus layer that guides the bacteria. Within the mucus layer, diffusion is effectively restricted, so that the concentration of most substances entering the mucus from the epithelial surface will remain constant through the entire width of the layer. Despite this, at least three chemical gradients are known to exist here: a proton (pH) gradient (2, 6), a bicarbonate͞CO 2 gradient (7,8), and, in the Helicobacter-infected mucosa, a urea͞ammonium gradient (9) created by bacterial urease. We hypothesized that H. pylori may use one or several of these transmucus gradients for orientation in vivo.We have previously developed a method to precisely determine the distribution and colonization density of Helicobacter felis in the gastric mucus of mice in vivo (3). This method uses a micromanipulator-controlled sampling device (10) to extract nanoliter samples from the mucus and mucosa of anesthetized animals. After immediate immobilization of the bacteria by cooling, the density and distribution of the bacteria can be studied by digital image processing.To identify gradients involved in the orientation of Helicobacter spp., we inverted or modified individual gradients in anesthetized H. pylori-infected Mongolian gerbils or H. felisinfected mice and studied the effect of these changes on the distribution of bacteria in the mucus layer. The data show that gastric Helicob...

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Section: Resultsmentioning

confidence: 99%

The spatial orientation of Helicobacter pylori in the gastric mucus

Schreiber

Konradt

Groll

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

288

261

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“…25,26,36,37 Drugs that are weak acids permeate and damage the epithelial cells more at lower luminal pH than in an alkaline environment. 38–40 Epithelial wound healing requires an alkaline surface pH both in the upper GI tract and in the colon. 25,26,41 Alkaline phosphatase ectoenzymatic activity is highly pH-sensitive and has recently been implicated in mucosal defense.…”

Section: Discussionmentioning

confidence: 99%

Loss of downregulated in adenoma (DRA) impairs mucosal HCO3− secretion in murine ileocolonic inflammation

Xiao

Juric

et al. 2012

Inflammatory Bowel Diseases

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Background Ileocolonic luminal pH has been reported to be abnormally low in inflammatory bowel disease (IBD) patients, and one of the causative factors may be reduced epithelial HCO3− secretory rate (JHCO3−). Disturbances in JHCO3− may occur due to inflammation-induced changes in the crypt and villous architecture, or due to the effect of proinflammatory cytokines on epithelial ion transporters. Methods To discriminate between these possibilities, the tumor necrosis factor alpha (TNF-α) overexpressing (TNF+/ΔARE) mouse model was chosen, which displays high proinflammatory cytokine levels in both ileum and colon, but develops only mild colonic histopathology and diarrhea. HCO3− secretion, mRNA expression, immunohistochemistry, and fluid absorptive capacity were measured in ileal and mid-colonic mucosa of TNF+/ΔARE and wildtype (WT) (TNF+/+) mice in Ussing chambers, and in anesthetized mice in vivo. Results The high basal JHCO3− observed in WT ileal and mid-colonic mucosa were luminal C1−-dependent and strongly decreased in TNF+/ΔARE mice. Downregulated in adenoma (DRA) mRNA and protein expression was strongly decreased in TNF+/ΔARE ileocolon, whereas cystic fibrosis transmembrane conductance regulator (CFTR), Na+/H+ exchanger 3 (NHE3), Na+/HCO3− cotransporter (NBC), and epithelial sodium channel (ENaC) expression was not significantly altered. This indicates that the severe defect in ileocolonic JHCO3− was due to DRA downregulation. Fluid absorption was severely depressed in the ileum but only mildly affected in the mid-distal colon, preventing the development of overt diarrhea. Conclusions Even mild ileocolonic inflammation may result in a decrease of epithelial HCO3− secretion, which may contribute to alterations in surface pH, intestinal flora, and mucus barrier properties.

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