Proximal tubular lactate transport in rat kidney: A micropuncture study

Höhmann, Bernhard; Frohnert, Peter P.; Kinne, Rolf; Baumann, Karl; Papavassiliou, Friderun; Wagner, M.

doi:10.1038/ki.1974.35

Cited by 43 publications

(22 citation statements)

References 43 publications

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“…But the present experimental data provide no information about whether this anion moiety represents HCOS-absorption due to H2COS recycling from lumen to cell (14), a direct HCOs-absorption process (13,20,41) (42,43), and it has been suggested that acetate, lactate, and pyruvate may be converted to acylglycines within renal tubular cells (44). Moreover, proximal tubular lactate absorption may depend on diffusion of lactate across luminal surfaces driven by lumen to cell lactate concentration gradients produced by cellular consumption of lactate (32). Consequently, it may be that in the present experiments (Table VII) KA,, exceeded KAC' because of preferential metabolic consumption of luminal rather than contraluminal acetate.…”

Section: Discussionmentioning

confidence: 49%

“…On the other hand, KACe' was calculated, as described previously (1), from the disappearance rates of ["C]acetate from luminal solutions. Thus, KA.e is a luminal efflux coefficient rather than a unidirectional lumen-to-bath flux coefficient, and may include not only terms for passive and/or active ["C]acetate flux from lumen to bath, and exchange diffusion of acetate, but also cellular consumption of luminal acetate (1), a phenomenon recently proposed on the basis of proximal tubular micropuncture studies in the rat to account for net luminal efflux of the organic anion lactate (32). Table VII shows that, in random paired observations in four tubules, KA.e was approximately three times greater than KAe', the mean paired difference between these values being 0.32±0.05 (P < 0.01).…”

Section: Introductionmentioning

confidence: 99%

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Anion transport processes in the mammalian superficial proximal straight tubule.

Schafer¹,

Andreoli²

1976

J. Clin. Invest.

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A B S T R A C T The experiments reported in this paper were designed to evaluate some of the characteristics of anion transport processes during fluid absorption from superficial proximal straight tubules isolated from rabbit kidney. We measured net chemical Cl-flux during fluid absorption from tubules perfused and bathed with Krebs-Ringer buffers containing 113.6 mM Cl-, 10 mM acetate, and 25 mM HCO3-at pH 7.4; assessed the effects of carbonic anhydrase inhibitors on net fluid absorption in the presence and absence of C02; and evaluated the influx and efflux coefficients for ["C]-acetate transport at 370C, at 210C, and in the presence of carbonic anhydrase inhibitors. The experimental data show that, for .this nephron segment, net Cl-flux accompanies approximately 27.5% of net Na+ absorption; and net Cl-absorption may be accounted for by a passive transport process, primarily diffusional in nature. Fluid absorption in this nephron segment is reduced 40-60% by carbonic anhydrase inhibitors, but only when the tubules are exposed to 95% 02-5% CO2 rather than 100% 02. Thus, it seems probable that approximately half of Na+ absorption in these tubules may be rationalized in terms of a carbonic anhydrasedependent C02 hydration process. In addition, there may occur in these isolated proximal tubules an acetazolamide-insensitive moiety of HC03-absorption comparable to that observed for proximal tubules in vivo. Finally, we provide evidence that net efflux of luminal acetate is due to metabolic energy-dependent processes

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Section: Discussionmentioning

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Anion transport processes in the mammalian superficial proximal straight tubule.

Schafer¹,

Andreoli²

1976

J. Clin. Invest.

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“…Even though the hybridization signals are more predominant in the cortex than in the medulla, detectable signals are present throughout the kidney, indicating that the transporter is expressed in most parts of the nephron. These findings are interesting, because micropuncture studies in rat kidney have shown that the absorption of lactate occurs predominantly in the proximal tubule (34). The most likely explanation for the differences between the in situ data and the micropuncture study is that the expression pattern of SMCT is heterogeneous among superficial nephrons, which are accessible for micropuncture studies and the nephrons present at deeper locations.…”

Section: Discussionmentioning

confidence: 65%

Expression of slc5a8 in Kidney and Its Role in Na+-coupled Transport of Lactate

Gopal¹,

Fei²,

Sugawara³

et al. 2004

Journal of Biological Chemistry

141

121

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We report here on the expression of slc5a8 in kidney and its relevance to Na ؉ -coupled reabsorption of lactate. slc5a8 is the murine ortholog of SLC5A8, a candidate tumor suppressor gene, which we recently cloned from human intestine and demonstrated its functional identity as a Na ؉ -coupled transporter for short-chain fatty acids and lactate. The slc5a8 cDNA, cloned from mouse kidney, codes for a protein consisting of 611 amino acids. When expressed heterologously in mammalian cells or Xenopus oocytes, slc5a8 mediates Na ؉ -coupled electrogenic transport of lactate/pyruvate as well as short-chain fatty acids (e.g. acetate, propionate, and butyrate). The Na ؉ /fatty acid stoichiometry varies depending on the fatty acid substrate (2:1 for lactate and 4:1 for propionate). This phenomenon of variable Na ؉ / substrate stoichiometry depending on the fatty acid substrate is also demonstrable with human SLC5A8. In situ hybridization with sagittal sections of mouse kidney demonstrates abundant expression of the transcripts in the cortex as well as the medulla. Brush border membrane vesicles prepared from rabbit kidney are able to transport lactate in a Na ؉ -coupled manner. The transport process exhibits the overshoot phenomenon, indicating uphill lactate transport in response to the transmembrane Na ؉ gradient. The Na ؉ -coupled lactate transport in these membrane vesicles is inhibitable by short-chain fatty acids. We conclude that slc5a8 is expressed abundantly in the kidney and that it plays a role in the active reabsorption of lactate. slc5a8 is the first transporter known to be expressed in mammalian kidney that has the ability to mediate the Na ؉ -coupled reabsorption of lactate.L-Lactate is present in blood at a concentration of ϳ90 mg/ liter (ϳ1.5 mM), but the urinary excretion of L-lactate is very low (100 -600 mg/day). With the normal glomerular filtration rate of 120 ml/min, the fractional reabsorption rate for L-lactate in mammalian kidney is Ͼ95% (1). The molecular identity of the transport system that is responsible for such an effective absorption process in the kidney has not yet been established. L-Lactate transport across mammalian cell plasma membrane is mediated by monocarboxylate transporters (MCTs) 1 (2, 3).MCTs are H ϩ -coupled transporters and, therefore, the direction of lactate flux in mammalian cells depends on the net chemical gradients for H ϩ and lactate across the membrane. The transport process is electroneutral because of the H ϩ / lactate stoichiometry of 1:1. There are several members within the MCT gene family that are expressed differentially in different tissues (2, 3). Many of the MCT gene family members are expressed in the kidney (2-5), but the exact locations of these transporters in terms of cell type and the apical membrane versus the basolateral membrane of the tubular cells are not known. Because the lumen-facing brush border membrane of the renal tubular cells mediates the first step in the reabsorption of solutes present in the glomerular filtrate, studies have been carr...

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“…In the clearance study of Rosin et al (42), increased Cl excretion became apparent only after significant volume expansion, which presumably depressed Cl reabsorption in the distal nephron to some extent (43), suggesting that the absence of a chloruresis in previous 2 The U/P Cl ratio of 1.24+0.01 in the presence of acidosis and a plasma HCO3 of 10.1+0.7 meq/liter might be explained by the increased reabsorption in the proximal tubule of other anionic species. There are indirect data to suggest that lactate, phosphate, and citrate reabsorption may be increased in the proximal tubule in acidosis (27)(28)(29)(30)(31)(32). studies must then be largely accounted for by enhanced Cl reabsorption in the loop of Henle, where active Cl transport takes place (18,19).…”

Section: Resultsmentioning

confidence: 99%

Effects of Acetazolamide on Proximal Tubule Cl, Na, and HCO3 Transport in Normal and Acidotic Dogs during Distal Blockade

Chou¹,

Porush²,

Slater³

et al. 1977

J. Clin. Invest.

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A B S T R A C T It has been suggested that the establishment of a tubular fluid to plasma chloride gradient in the late proximal tubule by the reabsorption of bicarbonate (and other anions) in the early proximal tubule is responsible for a significant part of sodium chloride and water reabsorption in the proximal tubule. In the present study the effects of acetazolamide on proximal tubule water and electrolyte excretion were examined in 6 normal dogs and 10 chronic ammonium chloride-loaded dogs during distal blockade produced by ethacrynic acid and chlorothiazide administration. During distal blockade control urine/plasma osmolality and urine/plasma sodium were close to unity in all experiments. Urine/plasma chloride and urine/plasma bicarbonate were 1.21+0.02 and 0.75+0.07 in normal and 1.24+0.01 and 0.04+0.01 in acidotic dogs, respectively. After the administration of acetazolamide (20 mg/kg i.v.), there was a significant increase in urine flow, absolute and fractional excretion of sodium, bicarbonate, and chloride in all animals. Associated with these effects, urine/plasma osmolality and urine/ plasma sodium remained unchanged but urine/plasma chloride decreased significantly to 1.15±0.01 in normal and to 1.19+0.01 in acidotic dogs. In acidotic dogs there was a significant correlation between the increase in bicarbonate, sodium, or chloride excretion after acetazolamide and the plasma bicarbonate level (range 6.8-12.5 meq/liter). These data demonstrate a significant effect of acetazolamide on bicarbonate, sodium, and chloride reabsorption in the proximal tubule even in the face of severe acidosis. Moreover, the data suggest that the decrease in chloride reabsorption (and accompanying sodium) after acetazolamide is related to the decrease in bicarbonate reabsorption and the associated decrease in the transtubular chloride gradient.

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Proximal tubular lactate transport in rat kidney: A micropuncture study

Cited by 43 publications

References 43 publications

Anion transport processes in the mammalian superficial proximal straight tubule.

Anion transport processes in the mammalian superficial proximal straight tubule.

Expression of slc5a8 in Kidney and Its Role in Na+-coupled Transport of Lactate

Effects of Acetazolamide on Proximal Tubule Cl, Na, and HCO3 Transport in Normal and Acidotic Dogs during Distal Blockade

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