Intracellular pH regulation in guinea-pig caecal and colonic enterocytes during and after loading with short-chain fatty acids and ammonia

Busche, Roger; Bartels, Jörg; Kirschberger, S; Engelhardt, W

doi:10.1007/s00424-002-0877-y

Cited by 12 publications

(79 citation statements)

References 45 publications

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“…The apical NH 4 ϩ inhibitory effect was not prevented by 100 M methazolamide, suggesting no role for apical carbonic anhydrase. However, apical NH 4 ϩ inhibition of current was prevented by 10 min of pretreatment of the apical surface with 500 M DIDS, 100 M 4,4Ј-dinitrostilbene-2,2Ј-disulfonic acid (DNDS), or 25 M niflumic acid, suggesting a role for NH 4 ϩ action through an apical anion exchanger. mRNA and protein for the apical anion exchangers SLC26A3 [downregulated in adenoma (DRA)] and SLC26A6 [putative anion transporter (PAT1)] were detected in T84 cells by RT-PCR and Northern and Western blots.…”

mentioning

confidence: 93%

“…mixtures, where K ϩ concentration ϩ [NH 4 ϩ ] ϭ 10 mM. The apical NH 4 ϩ inhibitory effect was not prevented by 100 M methazolamide, suggesting no role for apical carbonic anhydrase.…”

mentioning

confidence: 99%

“…CFTR, SLC26A3, SLC26A6, downregulated in adenoma, putative anion transporter 1 AMMONIUM (NH 4 ϩ ) concentration ([NH 4 ϩ ]) in the human colon ranges from 15 to 100 mM (41). Normal arterial plasma levels of NH 4 ϩ are relatively low, i.e., 45 M (10, 41).…”

mentioning

confidence: 99%

“…Normal arterial plasma levels of NH 4 ϩ are relatively low, i.e., 45 M (10, 41). The elevation of portal vein NH 4 ϩ levels with respect to arterial plasma (ϳ350 M) indicates net absorption of NH 4 ϩ across the colonic epithelium (41).…”

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confidence: 99%

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Apical ammonium inhibition of cAMP-stimulated secretion in T84 cells is bicarbonate dependent

Worrell

Best

Crawford

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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Normal human colonic luminal (NH 4 ϩ ) concentration ( [NH 4 ϩ ]) ranges from ϳ10 to 100 mM. However, the nature of the effects of NH 4 ϩ on transport, as well as NH 4 ϩ transport itself, in colonic epithelium is poorly understood. We elucidate here the effects of apical NH 4 ϩ on cAMP-stimulated Cl Ϫ secretion in colonic T84 cells. In HEPESbuffered solutions, 10 mM apical NH 4 ϩ had no significant effect on cAMP-stimulated current. In contrast, 10 mM apical NH 4 ϩ reduced current within 5 min to 61 Ϯ 4% in the presence of 25 mM HCO 3 Ϫ . Current inhibition was not simply due to an increase in extracellular K ϩ -like cations, in that the current magnitude was 95 Ϯ 5% with 10 mM apical K ϩ and 46 Ϯ 3% with 10 mM apical NH 4 ϩ relative to that with 5 mM apical K ϩ . We previously demonstrated that inhibition of Cl Ϫ secretion by basolateral NH 4 ϩ occurs in HCO 3 Ϫ -free conditions and exhibits anomalous mole fraction behavior. In contrast, apical NH 4 ϩ inhibition of current in HCO 3 Ϫ buffer did not show anomalous mole fraction behavior and followed the absolute [NH 4 ϩ ] in K ϩ -NH 4 ϩ mixtures, where K ϩ concentration ϩ [NH 4 ϩ ] ϭ 10 mM. The apical NH 4 ϩ inhibitory effect was not prevented by 100 M methazolamide, suggesting no role for apical carbonic anhydrase. However, apical NH 4 ϩ inhibition of current was prevented by 10 min of pretreatment of the apical surface with 500 M DIDS, 100 M 4,4Ј-dinitrostilbene-2,2Ј-disulfonic acid (DNDS), or 25 M niflumic acid, suggesting a role for NH 4 ϩ action through an apical anion exchanger. mRNA and protein for the apical anion exchangers SLC26A3 [downregulated in adenoma (DRA)] and SLC26A6 [putative anion transporter (PAT1)] were detected in T84 cells by RT-PCR and Northern and Western blots. DRA and PAT1 appear to associate with CFTR in the apical membrane. We conclude that the HCO 3 Ϫ dependence of apical NH 4 ϩ inhibition of secretion is due to the action of NH 4 ϩ on an apical anion exchanger.

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confidence: 93%

“…mixtures, where K ϩ concentration ϩ [NH 4 ϩ ] ϭ 10 mM. The apical NH 4 ϩ inhibitory effect was not prevented by 100 M methazolamide, suggesting no role for apical carbonic anhydrase.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Apical ammonium inhibition of cAMP-stimulated secretion in T84 cells is bicarbonate dependent

Worrell

Best

Crawford

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…85) The mechanisms responsible for the regulation of pH i seem to be localized at the basolateral membrane of enterocytes, and they consist mainly of Na ϩ /H ϩ and Cl Ϫ /HCO 3 Ϫ exchangers, 86) so it is expected that the pH o of the basolateral extracellular spaces undergoes significant changes during the transport of SCFAs. These changes in pH o could affect markedly weak electrolyte transport 87) and, on the other hand, could be deleterious to the cells of the surrounding environment.…”

Section: Is There a Ph O Microdomain At The Baso-lateral Aspect Of Comentioning

confidence: 99%

Extracellular pH in Restricted Domains as a Gating Signal for Ion Channels Involved in Transepithelial Transport

Sandoval

Burgos

Sepúlveda

et al. 2011

Biological & Pharmaceutical Bulletin

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The importance of intracellular pH (pH i ) in the regulation of diverse cellular activities ranging from cell proliferation and differentiation to cell cycle, migration and apoptosis has long been recognised. More recently, extracellular pH (pH o ), in particular that of relatively inaccessible compartments or domains that occur between cells in tissues, has begun to be acknowledged as a relevant signal in cell regulation. This should not be surprising given the abundant reports highlighting the pH o -dependence of the activity of membrane proteins facing the extracellular space such as receptors, transporters, ion channels and enzymes. Changes in pH affect the ionisation state of proteins through the effect on their titratable groups. There are proteins, however, which respond to pH shifts with conformational changes that are crucial for catalysis or transport activity. In such cases protons act as signalling molecules capable of eliciting fast and localised responses. We provide examples of ion channels that appear fastidiously designed to respond to extracellular pH in a manner that suggests specific functions in transporting epithelia. We shall also present ideas as to how these channels participate in complex transepithelial transport processes and provide preliminary experiments illustrating a new way to gauge pH o in confined spaces of native epithelial tissue.

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The effects of dietary phosphorus deficiency on surface pH and membrane composition of the mucosa epithelium in caprine jejunum

et al. 2006

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In ruminants, the uptake of inorganic phosphate (P(i)) across the intestinal mucosa epithelium by Na-dependent and Na-independent mechanisms is a main regulatory factor in P homeostasis. The aim of the study was to elucidate to which extent Na-independent mechanisms, including pH effects or composition of mucosal brush-border membranes, could be involved in positive stimulation of P(i) absorptive processes seen under the P deficient condition. Therefore, luminal, surface and intracellular pH of the jejunal epithelial cells in control and P depleted goats were compared and biochemical analyses of membrane phospholipids in the apical membrane of the jejunal epithelium were performed. Dietary P depletion resulted in decreased plasma P(i) levels. While pH in jejunal ingesta was not significantly changed, P depletion resulted in a significantly lower surface pH in the crypt region compared to control animals (7.62 +/- 0.02 vs. 7.77 +/- 0.04, n = 4, P < 0.01). Inhibition of apical Na(+)/H(+)-exchange resulted in an increase of the jejunal surface pH in P depleted animals by 0.07 +/- 0.01 (n = 6, P < 0.01) and 0.05 +/- 0.01 (n = 6, P < 0.01) for the villus and the crypt region, respectively. This increase were inversely correlated with the initial surface pH prior to inhibition. In contrast to surface pH, intracellular pH of the jejunal epithelium and the phospholipid composition of the apical jejunal membrane were not affected by P depletion. Although the data suggest the existence of a Na(+)/H(+)-exchange mechanism at the luminal surface of goat jejunum they do not support the hypothesis that adaptational processes of active P(i) absorption from goat jejunum in response to low dietary P could be based on "non P(i) transporter events".

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Intracellular pH regulation in guinea-pig caecal and colonic enterocytes during and after loading with short-chain fatty acids and ammonia

Cited by 12 publications

References 45 publications

Apical ammonium inhibition of cAMP-stimulated secretion in T84 cells is bicarbonate dependent

Apical ammonium inhibition of cAMP-stimulated secretion in T84 cells is bicarbonate dependent

Extracellular pH in Restricted Domains as a Gating Signal for Ion Channels Involved in Transepithelial Transport

The effects of dietary phosphorus deficiency on surface pH and membrane composition of the mucosa epithelium in caprine jejunum

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