Bicarbonate Secretion

Hj, Binder; Rajendran,; Sadasivan,; Jp, Geibel

doi:10.1097/01.mcg.0000155521.81382.3a

Cited by 47 publications

(14 citation statements)

References 39 publications

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“…These results are probably due to the dominant uptake of butyrate by SCFA/bicarbonate exchanger activity (34) and nonionic diffusion (35). Both uptake mechanisms are well described in colon although it is not clear to which proportion they contribute to colon butyrate uptake (36), because both pathways cannot be inhibited specifically.…”

Section: /Slc5a8mentioning

confidence: 89%

Lactaturia and Loss of Sodium-dependent Lactate Uptake in the Colon of SLC5A8-deficient Mice

Frank

Gröger

Diener

et al. 2008

Journal of Biological Chemistry

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SLC5A8 is a member of the sodium/glucose cotransporter family. It has been proposed that SLC5A8 might act as an apical iodide transporter in the thyroid follicular cells or as a transporter of short chain monocarboxylates. We have directly addressed the functional role of SLC5A8 in vivo by generation of SLC5A8 mutant mice. We found that SLC5A8 is responsible for the re-absorption of lactate at the apical membrane of the kidney proximal tubules and of serous salivary gland ducts. In addition, SLC5A8 mediated the uptake of lactate into colonocytes under physiological conditions. We did not find any evidence of SLC5A8 being essential for the apical iodide transport in the thyroid gland, even if the ion-cotransporter SLC26A4, causing the human Pendred syndrome, is missing. Because SLC5A8 is transcriptionally silenced in many tumors, it has been proposed that SLC5A8-mediated transport of butyrate suppresses tumor formation. Treatment of Slc5a8 ؊/؊ mice with carcinogens and breeding to the Apc min mouse line did not reveal a higher incidence of tumor formation. We conclude that SLC5A8 is instrumental in preventing lactaturia and loss of sodium-dependent uptake of lactate in the colon but does not have any apparent role in the prevention of tumor formation and growth.

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Section: /Slc5a8mentioning

confidence: 89%

Lactaturia and Loss of Sodium-dependent Lactate Uptake in the Colon of SLC5A8-deficient Mice

Frank

Gröger

Diener

et al. 2008

Journal of Biological Chemistry

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“…27 Intraluminal pH has been also found to be abnormally low in a number of studies in the colon of patients with UC, 28 but the importance of this has so far been discussed predominantly in the context of antiinflammatory drug release. 28 In the pancreas, however, ductal injury reduced

{HCO}_{3}^{-}

secretion and enhances the risk for acute pancreatitis.…”

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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“…These channels co-operate with the basolaterally located transporter, NKCC1, and play major roles in the secretion of Cl - [1,3]. In addition, Cl - /HCO 3 - transporters, such as DRA, are expressed at the apical membrane of human IECs [2,3,6], where their function is critically required for the electroneutral absorption of NaCl [1,4] and the secretion of HCO 3 - [3,5,7]. Thus, the concerted function of these channels and transporters is indispensable to maintain intestinal fluid homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Lineage-Specific Expression of Bestrophin-2 and Bestrophin-4 in Human Intestinal Epithelial Cells

et al. 2013

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Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3- or Cl-. Bestrophin genes represent a newly identified group of calcium-activated Cl- channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2 (BEST2) and bestrophin-4 (BEST4) might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression pattern along the gastrointestinal tract, or the lineage specificity of the cells expressing these genes, remains largely unknown. Here, we show that BEST2 and BEST4 are expressed in vivo, each in a distinct, lineage-specific manner, in human IECs. While BEST2 was expressed exclusively in colonic goblet cells, BEST4 was expressed in the absorptive cells of both the small intestine and the colon. In addition, we found that BEST2 expression is significantly down-regulated in the active lesions of ulcerative colitis, where goblet cells were depleted, suggesting that BEST2 expression is restricted to goblet cells under both normal and pathologic conditions. Consistently, the induction of goblet cell differentiation by a Notch inhibitor, LY411575, significantly up-regulated the expression of not BEST4 but BEST2 in MUC2-positive HT-29 cells. Conversely, the induction of absorptive cell differentiation up-regulated the expression of BEST4 in villin-positive Caco-2 cells. In addition, we found that the up- or down-regulation of Notch activity leads to the preferential expression of either BEST4 or BEST2, respectively, in LS174T cells. These results collectively confirmed that BEST2 and BEST4 could be added to the lineage-specific genes of humans IECs due to their abilities to clearly identify goblet cells of colonic origin and a distinct subset of absorptive cells, respectively.

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Bicarbonate Secretion

Cited by 47 publications

References 39 publications

Lactaturia and Loss of Sodium-dependent Lactate Uptake in the Colon of SLC5A8-deficient Mice

Lactaturia and Loss of Sodium-dependent Lactate Uptake in the Colon of SLC5A8-deficient Mice

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

Lineage-Specific Expression of Bestrophin-2 and Bestrophin-4 in Human Intestinal Epithelial Cells

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