Amiloride and the Na(+)/H(+) exchanger protein: mechanism and significance of inhibition of the Na(+)/H(+) exchanger (review).

Harris, Carmen V.; Fliegel, Larry

doi:10.3892/ijmm.3.3.315

Cited by 43 publications

(55 citation statements)

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“…The hydration of CO 2 by carbonic anhydrase generates both HCO 3 -and H + ions and the extrusion of the H + ions across the basolateral membrane by the Na + /H + exchanger NHE1, maintains the driving force for HCO 3 -secretion (Novak and Greger, 1988). However, 1 mmol l -1 serosal amiloride, which inhibits NHE1 activity (Harris and Fliegel, 1999), had little effect on the PGE 2 -stimulated increase in I sc (Fig. 4).…”

Section: The Pharmacology Of the Hco 3 -Secretory Responsementioning

confidence: 83%

Secretagogues stimulate electrogenic HCO3–secretion in the ileum of the brushtail possum,Trichosurus vulpecula:evidence for the role of a Na+/HCO3– cotransporter

Bartolo

Harfoot

Gill

et al. 2009

Journal of Experimental Biology

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SUMMARY Fluid secretion is essential for intestinal function and, in eutherian mammals, is driven by electrogenic Cl-transport, which is dependent upon a bumetanide-sensitive, basolateral Na-cotransporter, NKCC1. However, ileal secretion in the brushtail possum, a marsupial, involves a fundamentally different process, since NKCC1 expression is low in this tissue and the secretagogue-induced short circuit current (I sc ) is insensitive to bumetanide. In view of these differences we have investigated the basis of the secretory response of the possum ileum. In the Ussing chamber the secretory I sc is independent of Cl -but dependent upon Na

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Section: The Pharmacology Of the Hco 3 -Secretory Responsementioning

confidence: 83%

Secretagogues stimulate electrogenic HCO3–secretion in the ileum of the brushtail possum,Trichosurus vulpecula:evidence for the role of a Na+/HCO3– cotransporter

Bartolo

Harfoot

Gill

et al. 2009

Journal of Experimental Biology

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“…These pharmacological blockers are highly selective for their own channel system (20,37), which allows their actions to be studied separately.…”

Section: Discussionmentioning

confidence: 99%

Sodium channels are required during in vivo sodium chloride hyperosmolarity to stimulate increase in intestinal endothelial nitric oxide production

Zani

Bohlen

2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…We explored the possibility that exchange of cytosolic Na ϩ for luminal H ϩ accounted for at least part of the Golgi leak pathway. This was accomplished using amiloride, which is a potent inhibitor of several isoforms of the Na ϩ /H ϩ exchanger family (46). As reported in Table I, amiloride did not affect the resting pH of the Golgi and exerted no inhibition of the leak unmasked by concanamycin.…”

Section: Role Of Divalent Metal Hmentioning

confidence: 99%

Determinants of the pH of the Golgi Complex

Schapiro

Grinstein

2000

Journal of Biological Chemistry

122

111

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The factors contributing to the establishment of the steady state Golgi pH (pH G ) were studied in intact and permeabilized mammalian cells by fluorescence ratio imaging. Retrograde transport of the nontoxic B subunit of verotoxin 1 was used to deliver pH-sensitive probes to the Golgi complex. To evaluate whether counter-ion permeability limited the activity of the electrogenic V-ATPase, we determined the concentration of K ؉ in the lumen of the Golgi using a null point titration method. The [K ؉ ] inside the Golgi was found to be close to that of the cytosol, and increasing its permeability had no effect on pH G . Moreover, the capacity of the endogenous counter-ion permeability exceeded the rate of H ؉ pumping, implying that the potential across the Golgi membrane is negligible and has little influence on pH G . The V-ATPase does not reach thermodynamic equilibrium nor does it seem to be allosterically inactivated at the steady state pH G . In fact, active H ؉ pumping was detectable even below the resting pH G . A steady state pH was attained when the rate of pumping was matched by the passive backflux of H ؉ (equivalents) or "leak." The nature of this leak pathway was investigated in detail. Neither vesicular traffic nor H ؉ /cation antiporters or symporters were found to contribute to the net loss of H ؉ from the Golgi. Instead, the leak was sensitive to voltage changes and was inhibited by Zn 2؉ , resembling the H ؉ conductive pathway of the plasma membrane. We conclude that a balance between an endogenous leak, which includes a conductive component, and the H ؉ pump determines the pH at which the Golgi lumen attains a steady state.Stringent regulation of the internal pH of endomembrane compartments is required for their optimal function. In mitochondria, alkalinization of the matrix contributes to the generation of the transmembrane proton-motive force used to generate ATP (1). By contrast, luminal acidification is essential for the distribution and degradation of internalized ligands in the endocytic pathway (2-4), whereas it regulates post-translational modification and sorting of proteins along the secretory pathway (5-7). The pH varies in different subcompartments of the endocytic pathway, with acidification increasing progressively from the endocytic vesicles and early endosomes to late endosomes and ultimately lysosomes (8). Conversely, the pH of the secretory pathway becomes more acidic as the cargo travels toward the cell surface. Although the pH of the endoplasmic reticulum is thought to be near neutral (9, 10), acidification develops along the Golgi complex and is maximal at the transGolgi network (11-13). The development of such gradients appears to be important in targeting and retrieving components to and from individual subcompartments (6, 15). However, little is known about the determinants of pH in each subcompartment and particularly about the source of their differential acidification. In the case of the secretory pathway, this paucity of information is attributable, in part, to methodolo...

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Amiloride and the Na(+)/H(+) exchanger protein: mechanism and significance of inhibition of the Na(+)/H(+) exchanger (review).

Cited by 43 publications

References 0 publications

Secretagogues stimulate electrogenic HCO3–secretion in the ileum of the brushtail possum,Trichosurus vulpecula:evidence for the role of a Na+/HCO3– cotransporter

Secretagogues stimulate electrogenic HCO3–secretion in the ileum of the brushtail possum,Trichosurus vulpecula:evidence for the role of a Na+/HCO3– cotransporter

Sodium channels are required during in vivo sodium chloride hyperosmolarity to stimulate increase in intestinal endothelial nitric oxide production

Determinants of the pH of the Golgi Complex

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