scholarly journals Enzymatic and functional evidence for adaptation of the vacuolar H(+)-ATPase in proximal tubule apical membranes from rats with chronic metabolic acidosis.

1994 ◽  
Vol 269 (5) ◽  
pp. 3243-3250
Author(s):  
R. Chambrey ◽  
M. Paillard ◽  
R.A. Podevin
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Chronic Metabolic Acidosis ◽  
Apical Membranes

Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney

1996 ◽  
Vol 271 (4) ◽  
pp. F917-F925 ◽  
Author(s):  
P. M. Ambuhl ◽  
M. Amemiya ◽  
M. Danczkay ◽  
M. Lotscher ◽  
B. Kaissling ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Apical Membrane ◽  
Rat Kidney ◽  
Mrna Abundance ◽  
Thick Ascending Limb ◽  
Protein Abundance ◽  
Chronic Metabolic Acidosis ◽  
Apical Membranes

Chronic metabolic acidosis increases the activity of the proximal tubule apical membrane Na/H antiporter, which is encoded predominantly by the NHE3 isoform. The present studies examined the effect of chronic metabolic acidosis on apical membrane NHE3 protein abundance in rats. Rats subjected to NH4Cl in their drinking water developed a metabolic acidosis, which decreased in magnitude over 14 days. During this time, renal cortical brush-border membrane NHE3 protein abundance, assessed by Western blot, increased progressively (28% at 3 days, 59% at 7 days, and 90% at 14 days). Immunohistochemistry revealed that the acidosis-induced increase in NHE3 abundance occurred in the apical membranes of the S1 and S2 segments of the proximal tubule and the thick ascending limb. NHE3 mRNA abundance was not significantly increased in these animals, whereas phosphoenolpyruvate carboxykinase and glyceraldehyde-3-phosphate dehydrogenase mRNA abundances were significantly increased. These studies demonstrate that the increase in Na/H antiporter activity seen in metabolic acidosis involves an increase in NHE3 protein abundance, which is distributed along the proximal tubule and the thick ascending limb. In addition, these studies suggest that a component of this adaptation is unrelated to changes in NHE3 mRNA abundance.

Basolateral membrane H-OH-HCO3 transport in the proximal tubule

1989 ◽  
Vol 256 (5) ◽  
pp. F751-F765
Author(s):  
P. A. Preisig ◽  
R. J. Alpern
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Basolateral Membrane ◽  
Respiratory Acidosis ◽  
Cell Voltage ◽  
Transport Mechanisms ◽  
Transport Capacity ◽  
Chronic Metabolic Acidosis

This review focuses on the basolateral membrane mechanisms of H-OH-HCO3 transport in the proximal tubule. The mechanism that has the greatest transport capacity and mediates most of transepithelial H-HCO3 transport is the electrogenic, Na-3HCO3 cotransporter. This transporter has been extensively characterized in the salamander, rat, and rabbit proximal tubule, and has now been found in a number of other epithelia that effect transepithelial NaHCO3 transport. Transporter rate is sensitive to intra- and extracellular [Na], intra- and extracellular [HCO3]/pH, and cell voltage. Adaptations in transporter activity have been demonstrated in chronic metabolic acidosis and alkalosis, chronic respiratory acidosis and alkalosis, and chronic hyperfiltration. In addition to the Na-3HCO3 cotransporter, the basolateral membrane possesses both Na-dependent and -independent Cl-HCO3 exchangers, a H leak, and in the S3 proximal tubule an Na-H antiporter. The role of these H-OH-HCO3 transport mechanisms in transcellular HCO3 and Cl absorption and pHi defense is discussed.

scholarly journals Renal ATP Citrate Lyase (ATP CL) Protein Localizes throughout the Nephron and Increases Only in the Proximal Tubule with Chronic Metabolic Acidosis (CMA)

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 336A-336A
Author(s):  
Krishna Puttaparthi ◽  
Thomas Rogers ◽  
Nabil A Elshourbagy ◽  
Moshe Levi ◽  
Joel Z Melnick
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Atp Citrate Lyase ◽  
Chronic Metabolic Acidosis ◽  
Citrate Lyase

Effects of acid-base disturbances on renal handling of magnesium in the dog

1986 ◽  
Vol 70 (3) ◽  
pp. 277-284 ◽  
Author(s):  
Norman L. M. Wong ◽  
Gary A. Quamme ◽  
John H. Dirks
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Indirect Effect ◽  
Metabolic Alkalosis ◽  
Distal Tubule ◽  
Acid Base ◽  
Renal Handling ◽  
Chronic Metabolic Acidosis ◽  
Magnesium Transport

1. Clearance and micropuncture studies were performed in four groups of acutely thyropara-thyroidectomized animals to study the effects of alkalosis and acidosis on the renal handling of magnesium. 2. Our results indicate that chronic metabolic acidosis reduces, whereas acute metabolic alkalosis enhances, magnesium reabsorption. 3. The site within the nephron where absorption of magnesium increases or decreases during acid-base disturbances was beyond the late proximal tubule. 4. Tubular fluid bicarbonate was also measured in these experiments, and the results indicated that magnesium reabsorption in the distal tubule correlated to bicarbonate delivery. However, whether this was a direct or an indirect effect of bicarbonate on magnesium transport could not be delineated.

Determinants of ammonia entry along the rat proximal tubule during chronic metabolic acidosis

1989 ◽  
Vol 256 (6) ◽  
pp. F1104-F1110 ◽  
Author(s):  
E. E. Simon ◽  
C. Merli ◽  
J. Herndon ◽  
E. J. Cragoe ◽  
L. L. Hamm
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Significant Inhibition ◽  
Perfusion Rate ◽  
Chronic Metabolic Acidosis ◽  
Bicarbonate Reabsorption ◽  
Rate Dependent ◽  
Rat Proximal Tubule

The technique of in vivo microperfusion was used to examine the determinants of ammonia entry along the rat proximal tubule under conditions of chronic metabolic acidosis (CMA). When perfused with a 5 mM bicarbonate-containing perfusate, collected fluid ammonia concentrations remained constant with increasing flow rate and thus ammonia entry was highly flow-rate dependent. Ammonia entry was also flow-rate dependent using a 25 mM bicarbonate perfusate but entry reached a plateau as perfusion rate increased. Also, ammonia entry tended to be lower at all perfusion rates with the 25 mM perfusate compared with the 5 mM bicarbonate perfusate, but this was most evident at the highest perfusion rate (45 nl/min). The decline in ammonia entry was associated with increasing collected fluid bicarbonate concentrations, suggesting that there was inhibition of diffusion trapping of ammonia. The effects of Na+-H+ exchange inhibition on ammonia entry were examined using the amiloride analogue, 5-(N-ethyl-N-isopropyl)amiloride. With a 25 mM bicarbonate-containing perfusate, the amiloride analogue caused a significant decrease in bicarbonate reabsorption but a nonsignificant decrease in ammonia entry associated with a significant rise in collected fluid bicarbonate concentration. When the potential effects of decreased diffusion trapping of ammonia were eliminated with 12 and 5 mM bicarbonate-containing perfusates, the analogue had no effect on ammonia entry despite significant inhibition of bicarbonate reabsorption. Thus ammonia entry in CMA is moderately affected by tubule fluid pH but is highly flow-rate dependent. There were no effects of inhibition of Na+-H+ exchange above those expected from inhibition of diffusion trapping of ammonia.

Metabolic acidosis stimulates bicarbonate reabsorption in the early proximal tubule

1989 ◽  
Vol 257 (1) ◽  
pp. F35-F42 ◽  
Author(s):  
R. N. Santella ◽  
F. J. Gennari ◽  
D. A. Maddox
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Plasma Expansion ◽  
Plasma Volume Expansion ◽  
Major Site ◽  
Chronic Metabolic Acidosis ◽  
Bicarbonate Reabsorption ◽  
Filtered Load ◽  
Stimulation Of ◽  
Early Proximal Tubule

The early proximal tubule is the major site for renal bicarbonate reabsorption but little is known about the influence of acidosis on transport in this segment. This study examined early proximal bicarbonate reabsorption in rats with chronic metabolic acidosis (MA) (induced by NH4Cl administration). Rats were studied by free-flow micropuncture techniques, after varying degrees of plasma volume expansion to vary the filtered load of bicarbonate (FLHCO3). At FLHCO3 less than 700 pmol/min, both control and acidotic animals reabsorbed greater than 80% of the filtered load by 2 mm from Bowman's space. At higher FLHCO3 (700–1,100 pmol/min), reabsorption in the early proximal tubule was significantly greater in MA rats vs. control (633 +/- 26 vs. 449 +/- 24 pmol/min, between 1 and 2 mm from Bowman's space, P less than 0.001). This MA-induced stimulation of early proximal bicarbonate reabsorption was completely reversed by restoring systemic pH to normal either by acute hypocapnia or alkali infusion. Thus bicarbonate reabsorption in the early proximal tubule correlated closely with changes in systemic pH in rats with MA when bicarbonate delivery was increased by plasma expansion. The mechanism of this effect remains to be determined.

Increased Vmax for Na+/H+ antiporter activity in proximal tubule brush border vesicles from rabbits with metabolic acidosis

1984 ◽  
Vol 247 (2) ◽  
pp. F339-F343 ◽  
Author(s):  
C. J. Tsai ◽  
H. E. Ives ◽  
R. J. Alpern ◽  
V. J. Yee ◽  
D. G. Warnock ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Cation Exchange ◽  
Acridine Orange ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Co2 Concentration ◽  
Chronic Metabolic Acidosis ◽  
Experimental Animals ◽  
Renal Brush Border

Na+/H+ antiporter activity in renal brush border vesicles from control rabbits and rabbits made acidotic with 3 days of NH4Cl gavage was measured using the acridine orange method. Acidotic rabbits exhibited a significantly higher Vmax for antiporter activity (2.80 +/- 0.45 fluorescence units X s-1 X mg protein-1) compared with controls (1.31 +/- 0.13) but the Km for Na+ was unchanged (23.7 +/- 3.5 for acidotic, 19.1 +/- 3.2 mM for controls). When the Vmax for Na+/H+ antiporter activity was considered in relation to the degree of acidosis achieved in the experimental animals, there was a correlation (r = -0.75) between Vmax and plasma total CO2 concentration. Amiloride (100 microM) inhibited Na+/H+ exchange (Na+ = 90 mM) by 59 +/- 7% in both control and acidotic animals, indicating that the observed stimulation in Na+/H+ antiporter activity was not due to increased electrically coupled cation exchange. These findings suggest that the response of the proximal tubule to chronic metabolic acidosis involves an adaptive increase in the Vmax for Na+/H+ antiporter activity in the brush border membrane that is correlated to the degree of acidosis in the animals.

OKP cells express the Na-dicarboxylate cotransporter NaDC-1

2004 ◽  
Vol 287 (1) ◽  
pp. C64-C72 ◽  
Author(s):  
Seiji Aruga ◽  
Ana M. Pajor ◽  
Kiyoshi Nakamura ◽  
Liping Liu ◽  
Orson W. Moe ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Xenopus Oocytes ◽  
Fluorescent Protein ◽  
Stone Formation ◽  
Chronic Metabolic Acidosis ◽  
Opossum Kidney ◽  
Citrate Transport ◽  
Increased Risk ◽  
Green Fluorescent ◽  
Urinary Citrate

Urinary citrate concentration, a major factor in the formation of kidney stones, is primarily determined by its rate of reabsorption in the proximal tubule. Citrate reabsorption is mediated by the Na-dicarboxylate cotransporter-1 (NaDC-1). The opossum kidney (OKP) cell line possesses many characteristics of the renal proximal tubule. The OKP NaDC-1 (oNaDC-1) cDNA was cloned and encodes a 2.4-kb mRNA. When injected into Xenopus oocytes, the cotransporter is expressed and demonstrates Na-coupled citrate transport with a stoichiometry of ≥3 Na:1 citrate, specificity for di- and tricarboxylates, pH-dependent citrate transport, and pH-independent succinate transport, all characteristics of the other NaDC-1 orthologs. Chronic metabolic acidosis increases proximal tubule citrate reabsorption, leading to profound hypocitraturia and an increased risk for stone formation. Under the conditions studied, endogenous OKP NaDC-1 mRNA abundance is not regulated by changes in media pH. In OKP cells transfected with a green fluorescent protein-oNaDC-1 construct, however, media acidification increases Na-dependent citrate uptake, demonstrating posttranscriptional acid regulation of NaDC-1 activity.

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