Function of K+-Cl- Cotransporters in the Acid Secretory Mechanism of Gastric Parietal Cells

Fujii, Takuto; Fujita, Katsushi; Takeguchi, Noriaki; Sakai, Hideki

doi:10.1248/bpb.34.810

Cited by 13 publications

(7 citation statements)

References 24 publications

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“…The expression of these transporters has been documented in several epithelial cells either at the apical or basolateral membranes (17). Recent work has suggested an important role for KCC3 and KCC4 in acid secretion in the stomach (13)(14)(15). KCC3 knockout mice develop arterial hypertension (44), and KCC4 knockout mice exhibit renal tubular acidosis (6).…”

Section: Discussionmentioning

confidence: 99%

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Melo

Cruz-Rangel

Bautista

et al. 2013

American Journal of Physiology-Renal Physiology

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K+-Cl− cotransporter (KCC) isoforms 3 (KCC3) and 4 (KCC4) are expressed at the basolateral membrane of proximal convoluted tubule cells, and KCC4 is present in the basolateral membrane of the thick ascending loop of Henle's limb and α-intercalated cells of the collecting duct. Little is known, however, about the physiological roles of these transporters in the kidney. We evaluated KCC3 and KCC4 mRNA and protein expression levels and intrarenal distribution in male Wistar rats or C57 mice under five experimental conditions: hyperglycemia after a single dose of streptozotocin, a low-salt diet, metabolic acidosis induced by ammonium chloride in drinking water, and low- or high-K+ diets. Both KCC3 mRNA and protein expression were increased during hyperglycemia in the renal cortex and at the basolateral membrane of proximal tubule cells but not with a low-salt diet or acidosis. In contrast, KCC4 protein expression was increased by a low-sodium diet in the whole kidney and by metabolic acidosis in the renal outer medulla, specifically at the basolateral membrane of α-intercalated cells. The increased protein expression of KCC4 by a low-salt diet was also observed in WNK4 knockout mice, suggesting that upregulation of KCC4 in these circumstances is not WNK4 dependent. No change in KCC3 or KCC4 protein expression was observed under low- or high-K+ diets. Our data are consistent with a role for KCC3 in the proximal tubule glucose reabsorption mechanism and for KCC4 in salt reabsorption of the thick ascending loop of Henle's loop and acid secretion of the collecting duct.

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Section: Discussionmentioning

confidence: 99%

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Melo

Cruz-Rangel

Bautista

et al. 2013

American Journal of Physiology-Renal Physiology

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“…For this experiment, the intracellular TVs of gastric parietal cells were prepared from hog stomach. H + ,K + -ATPase, a nonelectrogenic H + ,K + antiporter, [20][21][22] is abundantly expressed in the TVs. 23) After the dissolution test for each tablet at pH 6.8 for 120 min, the dissolution media were sampled and then their efficacy for inhibiting the ATP-hydrolyzing activity of H + ,K + -ATPase was examined.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Gastric H+,K+-ATPase Activity in Vitro by Dissolution Media of Original Brand-Name and Generic Tablets of Lansoprazole, a Proton Pump Inhibitor

Phutthatiraphap

Hayashi

Fujii

et al. 2018

CHEMICAL & PHARMACEUTICAL BULLETIN

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To investigate the inhibitory effect of a commercial proton pump inhibitor (lansoprazole) on the gastric proton pump H,K-ATPase in vitro, we used orally disintegrating (OD) tablets including original brand-name and generic tablets. In the course of the development of generic products, dissolution and clinical tests are necessary to ensure their bioequivalence to the original brand-name products; by contrast, there is almost no opportunity to demonstrate their activity in vitro. This study initially compared the similarity of the dissolution of test generic tablets with that of the original brand-name tablets. The dissolution tests for 15 and 30-mg lansoprazole tablets found their dissolution properties were similar. Subsequently, the dissolution media were sampled and then their effects on the H,K-ATPase activity were measured using tubulovesicles prepared from the gastric mucosa of hogs. We confirmed that the inhibitory effects of the generic tablets on H,K-ATPase activity were consistent with those of the original brand-name tablets. Furthermore, lansoprazole contents in each tablet estimated from their inhibitory effects were in good agreement with their active pharmaceutical ingredient content. To our knowledge, this is the first technical report to compare the in vitro biochemical activity of lansoprazole OD tablets between the original brand-name and generic commercial products.

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“…Upon stimulation, H + ,K + ‐ATPase in both tubulovesicles and apical canalicular membrane is involved in massive gastric acid secretion. We found previously that KCC4 is predominantly expressed in the apical canalicular membrane of gastric parietal cells, and that its K + –Cl − cotransport is coupled with H + ,K + ‐ATPase activity in the membrane [11,12]. Because ERp57 is also associated with H + ,K + ‐ATPase at the canalicular membrane of parietal cells, it would be an interesting subject to clarify functional association between ERp57 and KCC4.…”

Section: Discussionmentioning

confidence: 95%

Modulation of H⁺,K⁺‐ATPase activity by the molecular chaperone ERp57 highly expressed in gastric parietal cells

et al. 2013

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Function of K+-Cl- Cotransporters in the Acid Secretory Mechanism of Gastric Parietal Cells

Cited by 13 publications

References 24 publications

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Inhibition of Gastric H<sup>+</sup>,K<sup>+</sup>-ATPase Activity <i>in Vitro</i> by Dissolution Media of Original Brand-Name and Generic Tablets of Lansoprazole, a Proton Pump Inhibitor

Modulation of H⁺,K⁺‐ATPase activity by the molecular chaperone ERp57 highly expressed in gastric parietal cells

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Function of K+-Cl- Cotransporters in the Acid Secretory Mechanism of Gastric Parietal Cells

Cited by 13 publications

References 24 publications

Molecular evidence for a role for K+-Cl− cotransporters in the kidney

Molecular evidence for a role for K+-Cl− cotransporters in the kidney

Inhibition of Gastric H<sup>+</sup>,K<sup>+</sup>-ATPase Activity <i>in Vitro</i> by Dissolution Media of Original Brand-Name and Generic Tablets of Lansoprazole, a Proton Pump Inhibitor

Modulation of H+,K+‐ATPase activity by the molecular chaperone ERp57 highly expressed in gastric parietal cells

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Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Modulation of H⁺,K⁺‐ATPase activity by the molecular chaperone ERp57 highly expressed in gastric parietal cells