Nongenomic stimulation of vacuolar H
            <sup>+</sup>
            -ATPases in intercalated renal tubule cells by aldosterone

Winter, Christian; Schulz, Nicole; Giebisch, Gerhard; Geibel, John P.; Wagner, Carsten A.

doi:10.1073/pnas.0307321101

Cited by 115 publications

(115 citation statements)

References 42 publications

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“…After washing, cells were excited with 490 and 440 nm light, while the emission was monitored at 535 nm. The ratiometric emission of 490͞440 was converted to intracellular pH after calibration (37) by using the high K ϩ ͞nigericin technique (38,39). In brief, after a 20 mM NH 4 Cl prepulse, cells were washed with a Na-free solution (Hepes buffer with NaCl replaced by of N-methyl-D-glucamine).…”

Section: Resultsmentioning

confidence: 99%

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Honegger

Capuano

Winter

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The Na + /H + exchanger 3 (NHE3) is expressed in the brush border membrane (BBM) of proximal tubules (PT). Its activity is down-regulated on increases in intracellular cAMP levels. The aim of this study was to investigate the contribution of the protein kinase A (PKA) and the exchange protein directly activated by cAMP (EPAC) dependent pathways in the regulation of NHE3 by adenosine 3′,5′-cyclic monophosphate (cAMP). Opossum kidney cells and murine kidney slices were treated with cAMP analogs, which selectively activate either PKA or EPAC. Activation of either pathway resulted in an inhibition of NHE3 activity. The EPAC-induced effect was independent of PKA as indicated by the lack of activation of the kinase and the insensitivity to the PKA inhibitor H89. Both PKA and EPAC inhibited NHE3 activity without inducing changes in the expression of the transporter in BBM. Activation of PKA, but not of EPAC, led to an increase of NHE3 phosphorylation. In contrast, activation of PKA, but not of EPAC, inhibited renal type IIa Na + -coupled inorganic phosphate cotransporter (NaPi-IIa), another Na-dependent transporter expressed in proximal BBM. PKA, but not EPAC, induced the retrieval of NaPi-IIa from BBM. Our results suggest that EPAC activation may represent a previously unrecognized mechanism involved in the cAMP regulation of NHE3, whereas regulation of NaPi-IIa is mediated by PKA but not by EPAC.

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Section: Resultsmentioning

confidence: 99%

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Honegger

Capuano

Winter

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Single cortical CD fragments of 6-week-old mouse kidneys were selected under microscopic examination after collagenase digestion by morphologic criteria as described (18). Fragments were mounted in a perfusion chamber and acidified by using the NH 4 Cl (20 mM) prepulse technique, and intracellular pH (pH i ) of single ICs was monitored by using the pH-sensitive dye BCECF as described (19). Groups were compared by using the unpaired Student t test.…”

Section: Surgical Methodsmentioning

confidence: 99%

The B1-subunit of the H⁺ATPase is required for maximal urinary acidification

Finberg

Wagner

Bailey

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The multisubunit vacuolar-type H ؉ ATPases mediate acidification of various intracellular organelles and in some tissues mediate H ؉ secretion across the plasma membrane. Mutations in the B1-subunit of the apical H ؉ ATPase that secretes protons in the distal nephron cause distal renal tubular acidosis in humans, a condition characterized by metabolic acidosis with an inappropriately alkaline urine. To examine the detailed cellular and organismal physiology resulting from this mutation, we have generated mice deficient in the B1-subunit (Atp6v1b1 ؊/؊ mice). Urine pH is more alkaline and metabolic acidosis is more severe in Atp6v1b1 ؊/؊ mice after oral acid challenge, demonstrating a failure of normal urinary acidification. In Atp6v1b1 ؊/؊ mice, the normal urinary acidification induced by a lumen-negative potential in response to furosemide infusion is abolished. After an acute intracellular acidification, Na ؉ -independent pH recovery rates of individual Atp6v1b1 ؊/؊ intercalated cells of the cortical collecting duct are markedly reduced and show no further decrease after treatment with the selective H ؉ ATPase inhibitor concanamycin. Apical expression of the alternative B-subunit isoform, B2, is increased in Atp6v1b1 ؊/؊ medulla and colocalizes with the H ؉ ATPase E-subunit; however, the greater severity of metabolic acidosis in Atp6v1b1 ؊/؊ mice after oral acid challenge indicates that the B2-subunit cannot fully functionally compensate for the loss of B1. Our results indicate that the B1 isoform is the major B-subunit isoform that incorporates into functional, plasma membrane H ؉ ATPases in intercalated cells of the cortical collecting duct and is required for maximal urinary acidification.collecting duct ͉ intercalated cell ͉ pH homeostasis ͉ renal tubular acidosis ͉ vacuolar H ϩ ATPase

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“…25,31,52 BCECF AM (1 M; Molecular Probes, Invitrogen AG, Basel, Switzerland) was used to monitor pH i . Cells were acidified using the NH 4 Cl (20 mM) prepulse technique, as described previously.…”

Section: Tubule Preparations and Ph I Measurementsmentioning

confidence: 99%

“…Cells were acidified using the NH 4 Cl (20 mM) prepulse technique, as described previously. 52 Please see supplemental information for detailed methods.…”

Section: Tubule Preparations and Ph I Measurementsmentioning

confidence: 99%

The Calcium-Sensing Receptor Promotes Urinary Acidification to Prevent Nephrolithiasis

Renkema¹,

Velić²,

Dijkman³

et al. 2009

Journal of the American Society of Nephrology

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Nongenomic stimulation of vacuolar H ⁺ -ATPases in intercalated renal tubule cells by aldosterone

Cited by 115 publications

References 42 publications

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

The B1-subunit of the H⁺ATPase is required for maximal urinary acidification

The Calcium-Sensing Receptor Promotes Urinary Acidification to Prevent Nephrolithiasis

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Nongenomic stimulation of vacuolar H + -ATPases in intercalated renal tubule cells by aldosterone

Cited by 115 publications

References 42 publications

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

The B1-subunit of the H+ATPase is required for maximal urinary acidification

The Calcium-Sensing Receptor Promotes Urinary Acidification to Prevent Nephrolithiasis

Contact Info

Product

Resources

About

Nongenomic stimulation of vacuolar H ⁺ -ATPases in intercalated renal tubule cells by aldosterone

The B1-subunit of the H⁺ATPase is required for maximal urinary acidification