Parallel adaptation of the rabbit renal cortical sodium/proton antiporter and sodium/bicarbonate cotransporter in metabolic acidosis and alkalosis.

Akiba, Takashi; Rocco, Vito K.; Warnock, David G.

doi:10.1172/jci113074

Cited by 119 publications

(106 citation statements)

References 41 publications

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“…In the renal proximal tubule this is associated with growth, an increased capacity for H secretion, and increased ammonia synthesis. The Vmax of the apical membrane Na/H antiporter and the basolateral membrane Na/HCO3/CO3 cotransporter, and activities of three ammoniagenic enzymes, phosphate-dependent glutaminase, glutamate dehydrogenase, and phosphoenolpyruvate carboxykinase, are all increased ( [1][2][3][4][5]. Acid incubation of cultured renal cells (primary cultures, MCT, OKP, LLC-PK1) causes an increase in Na/H antiporter activity at 24-48 h that is dependent on protein synthesis, and is associated with an increase in Na/H antiporter mRNA (NHE-1 isoform; MCT, LLC-PK1) (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Acid activation of immediate early genes in renal epithelial cells.

Yamaji¹,

Moe²,

Miller³

et al. 1994

J. Clin. Invest.

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These studies examined the effect of acidosis on immediate early (IE) gene expression in renal tubule cells. In MCT cells, an SV40 transformed mouse proximal tubule cell line, incubation in acid media led to transient increases in c-fos, c-jun, junB, and egr-1 mRNA abundance, peking at 30 min to 1 h. In vivo metabolic acidosis caused more prolonged increases in these mRNA species in renal cortex. Nuclear runon studies demonstrated increased rates of transcription for these IE genes. In addition, pretreatment of cells with cycloheximide caused superinduction of these mRNA by acid incubation. These responses are similar to those elicited by growth factors. Inhibition of tyrosine kinase pathways prevented IE gene activation by acid, while inhibition of protein kinase C and/or increases in cell calcium had no effect. In 3T3 cells, acid activated IE genes by a different mechanism in that the increase in mRNA did not include cjun, was more prolonged, and was blocked by cycloheximide. In summary, incubation of renal cells in acid media leads to activation of IE genes that is similar to growth factor-induced IE gene activation, and is likely mediated by tyrosine kinase pathways. (J. Clin. Invest. 1994. 94:1297-1303

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Section: Introductionmentioning

confidence: 99%

Acid activation of immediate early genes in renal epithelial cells.

Yamaji¹,

Moe²,

Miller³

et al. 1994

J. Clin. Invest.

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“…One component of this response is an increase in the activities of the proximal tubule apical membrane Na/H antiporter and basolateral membrane Na/ 3HC03 symporter, the major proximal tubule H/HCO3 transporter mechanisms (1)(2)(3)(4)(5). The transporter effects appear kinetically as Vmax effects and persist when the transporter is studied outside the acidotic milieu.…”

mentioning

confidence: 99%

Preincubation in acid medium increases Na/H antiporter activity in cultured renal proximal tubule cells.

Horie

Moe

Tejedor

et al. 1990

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

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Chronic acidosis in vivo leads to an increase in proximal tubule Na/H antiporter activity that persists when the transporter is studied out of the acidotic environment. It is presently not clear whether a decrease in extracellular fluid pH alone is sufficient to elicit this adaptation. The present studies examined the effect of acid preincubation on Na/H antiporter activity in cultured proximal tubule cells. Antiporter activity was examined after a 2-day preincubation in control or acid medium, 1 hr after removal from the preincubation fluid.Na/H antiporter activity was assayed as the initial rate of (vol/vol) to the culture medium for the first 3 days to allow better cell attachment. After achieving confluence (8-12 days), cells were rendered quiescent by removal of insulin and hydrocortisone for 48 hr prior to and during preincubation (10).Cultured fibroblasts were derived from human foreskin and used in passages 5-7 (11). Fibroblasts were grown on glass coverslips in DMEM supplemented with penicillin (100 units/ ml), streptomycin (100 ,ug/ml), and 10% fetal bovine serum. Fibroblasts were incubated with a reduced concentration of fetal bovine serum (1%) for 24 hr prior to and during preincubation.Measurement of Intracellular pH and Na/H Antiporter Activity. Continuous measurement of cytoplasmic pH (pHi) was accomplished using the intracellularly trapped pHsensitive dye 2',7'-bis(2-carboxyethyl)-5-(and -6)carboxyfluorescein (BCECF acid). Cells were loaded with the acetoxymethyl ester of BCECF (10 ,uM)

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“…[44][45][46] Chronic adaptation of NHE3 has been described in both the proximal tubule (increased NHE3 activity and protein) and TAL (increased NHE3 protein and transcript) in animals given a sufficient acid load to chronically suppress serum [HCO 3 − ]. 36,[47][48][49][50][51][52][53] Presently it is unclear whether the signals and mechanisms responsible for increased NHE3 are the same for the proximal tubule and TAL. The subsequent discussion focuses only on proximal tubule NHE3.…”

Section: Adaptation To Metabolic Acidosismentioning

confidence: 99%

Na+/H+ Exchangers in Renal Regulation of Acid-Base Balance

Bobulescu

Moe

2006

Seminars in Nephrology

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The kidney plays key roles in extracellular fluid pH homeostasis by reclaiming bicarbonate (HCO 3 − ) filtered at the glomerulus and generating the consumed HCO 3 − by secreting protons (H + ) into the urine (renal acidification). Sodium-proton exchangers (NHEs) are ubiquitous transmembrane proteins mediating the countertransport of Na + and H + across lipid bilayers. In mammals, NHEs participate in the regulation of cell pH, volume, and intracellular sodium concentration, as well as in transepithelial ion transport. Five of the 10 isoforms (NHE1-4 and NHE8) are expressed at the plasma membrane of renal epithelial cells. The best-studied isoform for acid-base homeostasis is NHE3, which mediates both HCO 3 − absorption and H + excretion in the renal tubule. This article reviews some important aspects of NHEs in the kidney, with special emphasis on the role of renal NHE3 in the maintenance of acid-base balance.Keywords sodium/hydrogen exchange; renal acidification; bicarbonate absorption The free hydrogen ion (H + ) concentration in body fluids is regulated exquisitely around 40 nmol/L (pH 7.40) whereas H + flux through the body greatly exceeds this magnitude. In a 70-kg human being at a basal state, normal metabolic and dietary acid production rate is about 50 to 70 mmoles/d and respiratory volatile acid production at the basal state is around 15,000 mmoles/d, with peak production at maximal exercise reaching 200 mmoles/min. The flux of H + through the organism over 24 hours is 8 orders of magnitude greater than the total pool of free H + in total body water (<2 μmoles). This remarkable homeostatic feat is accomplished by concerted efforts of extracellular and intracellular buffers, highly efficient ventilatory responses, metabolic functions of the liver, and renal ammoniagenic and solute transport mechanisms. For excretion of nonvolatile acid and base loads, the kidney assumes the pivotal role.A filtration-reabsorption nephron bears an exorbitant burden of having to reclaim a vast amount of valuable solutes indiscriminately dispensed in the filtrate; one of which of course is the approximately 4,000 mmoles of bicarbonate (HCO 3 − ) per day. The luminal acid disequilibrium pH implies that the predominant mode of HCO 3 − absorption involves H + secretion, although a small concomitant degree of direct HCO 3 − reabsorption cannot be excluded. 1 Two points are noteworthy. First, complete reclamation of the approximately 4,000 mmoles of filtered HCO 3 − forestalls a physiologic disaster but does not lead to net acid secretion. Further elaboration of H + into the urine is necessary. Second, whether the organism is catering to the The era of phenomenologic analysis was supplemented by gene-and protein-specific reagents when the first mammalian NHE was cloned by Sardet et al. 7 The relationship between mammalian NHE genetic sequence and those from a multitude of organisms is shown in Fig 2. Na + /H + exchange across lipid bilayers and proteins that sustain this function are universal in prokaryotic, animal, and...

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Parallel adaptation of the rabbit renal cortical sodium/proton antiporter and sodium/bicarbonate cotransporter in metabolic acidosis and alkalosis.

Cited by 119 publications

References 41 publications

Acid activation of immediate early genes in renal epithelial cells.

Acid activation of immediate early genes in renal epithelial cells.

Preincubation in acid medium increases Na/H antiporter activity in cultured renal proximal tubule cells.

Na+/H+ Exchangers in Renal Regulation of Acid-Base Balance

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