<i>Helicobacter pylori</i>Vacuolating Cytotoxin Inhibits Duodenal Bicarbonate Secretion by a Histamine‐Dependent Mechanism in Mice

Tuo, Biguang; Song, Penghong; Wen, Ge; Sewald, Xaver; Gebert-Vogl, Bettina; Haas, Rainer; Mann, Michael P.; Seidler, Ursula

doi:10.1086/596318

Cited by 13 publications

(4 citation statements)

References 39 publications

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“…The antibody-based procedures used in this study comply with the recommendations made by the British Journal of Pharmacology. Immunohistocytochemistry was carried out as described previously (Tuo et al, 2009). Briefly, the slides with jejunal tissues from C57BL/6 mice or with IECs were incubated with an anti-STIM1…”

Section: Immunohistocytochemistrymentioning

confidence: 99%

Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca²⁺ entry mechanisms

Zhang

Wan

Chu

et al. 2020

British J Pharmacology

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Background and Purpose: Luminal glucose enhances intestinal Ca 2+ absorption through apical Ca v 1.3 channels necessary for GLUT2-mediated glucose absorption. As these reciprocal mechanisms are not well understood, we investigated the regulatory mechanisms of intestinal [Ca 2+ ] cyt and SGLT1-mediated Na +-glucose co-transports. Experimental Approach: Glucose absorption and channel expression were examined in mouse upper jejunal epithelium using an Ussing chamber, immunocytochemistry and Ca 2+ and Na + imaging in single intestinal epithelial cells. Key Results: Glucose induced jejunal I sc via Na +-glucose cotransporter 1 (SGLT1) operated more efficiently in the presence of extracellular Ca 2+. A crosstalk between luminal Ca 2+ entry via plasma Ca v 1.3 channels and the ER Ca 2+ release through ryanodine receptor (RYR) activation in small intestinal epithelial cell (IEC) or Ca 2+-induced Ca 2+ release (CICR) mechanism was involve in Ca 2+-mediated jejunal glucose absorption. The ER Ca 2+ release through RyR triggered basolateral Ca 2+ entry or store-operated Ca 2+ entry (SOCE) mechanism and the subsequent Ca 2+ entry via Na + /Ca 2+ exchanger 1 (NCX1) were found to be critical in Na +-glucose cotransporter-mediated glucose absorption. Blocking RyR, SOCE and NCX1 inhibited glucose induced [Na + ] cyt and [Ca 2+ ] cyt in single IEC and protein expression and co-localization of STIM1/Orai1, RyR1 and NCX1 were detected in IEC and jejunal mucosa. Conclusion and Implications: Luminal Ca 2+ influx through Ca v 1.3 triggers the CICR through RyR1 to deplete the ER Ca 2+ , which induces the basolateral STIM1/Orai1-mediated SOCE mechanism and the subsequent Ca 2+ entry via NCX1 to regulate intestinal glucose uptake via Ca 2+ signalling. Targeting these mechanisms in IEC may help to modulate blood glucose and sodium in the metabolic disease. Abbreviations: [Ca 2+ ]cyt, cytosolic Ca 2+ concentration; [Na + ]cyt, cytosolic Na + concentration; 2-APB, 2-aminoethoxydiphenyl borate; CICR, Ca 2+-induced Ca 2+ release; CIRC, calcium-induced calcium release; ER, endoplasmic reticulum; IEC, intestinal epithelial cells; I sc , short-circuit current; NCX1, Na + /Ca 2+ exchanger 1; RyR, ryanodine receptor; SOCE, store-operated Ca 2+ entry; STIM1, stromal interaction molecule 1; TPEN, N,N,N 0 ,N 0-tetrakis(2-pyridylmethyl) ethylenediamine. Fenglian Zhang and Hanxing Wan equally contributed to this work.

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Section: Immunohistocytochemistrymentioning

confidence: 99%

Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca²⁺ entry mechanisms

Zhang

Wan

Chu

et al. 2020

British J Pharmacology

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“…Through the p38/ATF-2 cascade, COX-2 is upregulated, which leads to increased production of prostaglandin E 2 (PGE 2 ; Hisatsune et al, 2007). Conversely, in mice VacA inhibits PGE 2 -stimulated duodenal epithelial bicarbonate (

{HCO}_{3}^{-}

) secretion by inducing the release of mucosal histamine (Tuo et al, 2009). While the reason for this discrepancy in VacA mediated increase in PGE 2 effects is unclear, it should be noted that decreased duodenal epithelial

{HCO}_{3}^{-}

secretion is associated with duodenal ulcers and may leave the mucosal layer less able to repair itself (Isenberg et al, 1987).…”

Section: Vaca Functionsmentioning

confidence: 99%

A Tale of Two Toxins: Helicobacter Pylori CagA and VacA Modulate Host Pathways that Impact Disease

2010

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Helicobacter pylori is a pathogenic bacterium that colonizes more than 50% of the world's population, which leads to a tremendous medical burden. H. pylori infection is associated with such varied diseases as gastritis, peptic ulcers, and two forms of gastric cancer: gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. This association represents a novel paradigm for cancer development; H. pylori is currently the only bacterium to be recognized as a carcinogen. Therefore, a significant amount of research has been conducted to identify the bacterial factors and the deregulated host cell pathways that are responsible for the progression to more severe disease states. Two of the virulence factors that have been implicated in this process are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA), which are cytotoxins that are injected and secreted by H. pylori, respectively. Both of these virulence factors are polymorphic and affect a multitude of host cellular pathways. These combined facts could easily contribute to differences in disease severity across the population as various CagA and VacA alleles differentially target some pathways. Herein we highlight the diverse types of cellular pathways and processes targeted by these important toxins.

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“…Considering the findings in the present study, it is assumed that beyond treatment of constipation, irritable bowel syndrome and enteropathy, lubiprostone may have potential to be used more for protection against gastritis and peptic ulcer diseases, since it does stimulate the secretion of HCO 3 in both the stomach and duodenum. Furthermore, because duodenal HCO 3 secretion was shown to be impaired in patients with Helicobacter pylori (Tuo et al 2004;Tuo et al 2009), it is also possible that lubiprostone may be useful for treatment of Helicobater pylorirelated diseases. K. Takeuchi, S. Hayashi, K. Amagase…”

Section: Discussionmentioning

confidence: 99%

Stimulation of gastroduodenal HCO3- secretion by lubiprostone mediated by different prostaglandin EP receptor subtypes

Takeuchi

Hayashi

Amagase

2020

Integrative Physiology

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We examined the stimulatory effects of lubiprostone, a bicyclic fatty acid derived from prostaglandin E 1 and a chloride channel type-2 opener (ClC-2), on HCO 3-secretion in the rat stomach and duodenum, with a focus on the EP receptor subtypes involved in this action. Under urethane anesthesia, an ex-vivo chambered stomach or a duodenal loop was perfused with saline, and HCO 3-secretion was measured at pH 7.0 using a pH stat-method. Lubiprostone (0.1-30 µM) was perfused in the chamber or loop for 10 min. Indomethacin, ONO-8711 (an EP 1 antagonist), or AE5-599 (an EP 3 antagonist) was given s.c. 1 h before the lubiprostone treatment, while AE3-208 (an EP 4 antagonist) or CFTR inh-172 (a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor) was given i.p. 30 min before. Lubiprostone dosedependently and significantly increased HCO 3-secretion in both the stomach (≥ 10 µM) and duodenum (≥ 1 µM). The stimulatory effect in the stomach was significantly abrogated by a pretreatment with the EP 1 antagonist, but not the EP 3 /EP 4 antagonists or CFTR inhibitor, while that in the duodenum was significantly attenuated by the EP 3 /EP 4 antagonists as well as the CFTR inhibitor. Indomethacin had no effect on the response of either tissue to lubiprostone. These results suggest that lubiprostone stimulated HCO 3secretion in the stomach and duodenum in a manner that was mediated by different EP receptor subtypes; the former was mediated by EP 1 receptors, while the latter was mediated by both EP 3 and EP 4 receptors. CFTR/ClC-2 may be involved in the response observed in the duodenum, but not in the stomach.

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Helicobacter pyloriVacuolating Cytotoxin Inhibits Duodenal Bicarbonate Secretion by a Histamine‐Dependent Mechanism in Mice

Abstract: H. pylori VacA inhibits PGE2-stimulated duodenal epithelial HCO3- secretion by a histamine-dependent mechanism. This effect likely contributes to the damaging effect of H. pylori in the duodenal mucosa.

Cited by 13 publications

References 39 publications

Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca²⁺ entry mechanisms

Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca²⁺ entry mechanisms

A Tale of Two Toxins: Helicobacter Pylori CagA and VacA Modulate Host Pathways that Impact Disease

Stimulation of gastroduodenal HCO3- secretion by lubiprostone mediated by different prostaglandin EP receptor subtypes

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Helicobacter pyloriVacuolating Cytotoxin Inhibits Duodenal Bicarbonate Secretion by a Histamine‐Dependent Mechanism in Mice

Abstract: H. pylori VacA inhibits PGE2-stimulated duodenal epithelial HCO3- secretion by a histamine-dependent mechanism. This effect likely contributes to the damaging effect of H. pylori in the duodenal mucosa.

Cited by 13 publications

References 39 publications

Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca2+ entry mechanisms

Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca2+ entry mechanisms

A Tale of Two Toxins: Helicobacter Pylori CagA and VacA Modulate Host Pathways that Impact Disease

Stimulation of gastroduodenal HCO3- secretion by lubiprostone mediated by different prostaglandin EP receptor subtypes

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About

Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca²⁺ entry mechanisms

Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca²⁺ entry mechanisms