Ammoniagenesis by the Isolated Perfused Rat Kidney: The Critical Role of Urinary Acidification

Tannen, Richard L.; Ross, Brian D.

doi:10.1042/cs0560353

Cited by 42 publications

(13 citation statements)

References 26 publications

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“…Thus, metabolic acidosis induces a precocious adaptation of renal ammoniagenesis and, consequently, larger amounts of buffer become available to meet the greater need to excrete fixed acids. Recent studies in the isolated perfused rat kidney have indicated that the fall of urine pH, rather than the decrease of HCO-in the perfusion fluid, is the critical stimulus for increased ammonia production (25). Conversely, results reported here suggest that, in man, at the onset of metabolic acidosis, the degree of acidosis and the changes in urine flow, rather than the fall of urine pH, are the major factors stimulating the increase in ammonia production.…”

Section: Resultscontrasting

confidence: 50%

“…It is poorly understood if, and to what extent, these factors are able to stimulate renal ammonia production. Acidemia seems to be the major factor increasing ammonia production in the intact rat (17), whereas urine pH has a critical role in increasing ammoniagenesis in isolated perfused kidney preparations (25). In vitro studies, on the other hand, demonstrate that ammonia production from glutamine by both rat renal tissue slices and isolated mitochondria is unmodified or reduced (26)(27)(28)(29)(30)(31)(32) when an acidic incubation medium (pH 7.0) is used.…”

Section: Introductionmentioning

confidence: 99%

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Renal ammoniagenesis in an early stage of metabolic acidosis in man.

Tizianello¹,

Garibotto²,

Robaudo³

et al. 1982

J. Clin. Invest.

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A B S T R A C T Total renal ammonia production and ammonia precursor utilization were evaluated in patients under normal acid-base balance and in patients with 24-h NH4C1 acidosis by measuring (a) ammonia excreted with urine and that added to renal venous blood, and (b) amino acid exchange across the kidney. In 24-h acidosis not only urinary ammonia excretion is increased, but also total ammonia production is augmented (P < 0.005) in comparison with controls. By evaluating the individual role of acid-base parameters, urine pH and urine flow in influencing renal ammonia production, it was shown that the degree of acidosis and urine flow are likely major factors stimulating ammoniagenesis. Both urine pH and urine flow are determinant in the preferential shift of ammonia into urine. In 1-d acidosis, renal extraction of glutamine was not increased and the total ammonia produced/ glutamine N extracted ratio was higher than in controls (P < 0.005) and was inversely correlated with the log of arterial bicarbonate concentration (P < 0.001). In the same condition, renal glycine and ornithine uptake took place; the more severe the acidosis, the greater was the renal extraction of these amino acids (P < 0.001). These data indicate that at the early stages of metabolic acidosis, in spite of a brisk increase in ammonia production, the mechanisms responsible for the increased glutamine use, which are operative in chronic acidosis, are not activated and other ammonia precursors, besides glutamine, are probably used for ammonia production.

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Section: Resultscontrasting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Renal ammoniagenesis in an early stage of metabolic acidosis in man.

Tizianello¹,

Garibotto²,

Robaudo³

et al. 1982

J. Clin. Invest.

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“…Additional responses include a prompt acidification of the urine that results from translocation, as evidenced in OKP cells (67), and by acute activation of NHE3 (68). This process facilitates the rapid removal of cellular ammonium ions (69) and ensures that the bulk of the ammonium ions generated from the amide and amine nitrogens of glutamine are excreted in the urine. Finally, the cellular concentrations of glutamate and a-ketoglutarate are significantly decreased within the rat renal cortex (70).…”

Section: Response To Acidosismentioning

confidence: 99%

Proximal Tubule Function and Response to Acidosis

Curthoys

Moe

2014

Clinical Journal of the American Society of Nephrology

239

171

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SummaryThe human kidneys produce approximately 160-170 L of ultrafiltrate per day. The proximal tubule contributes to fluid, electrolyte, and nutrient homeostasis by reabsorbing approximately 60%-70% of the water and NaCl, a greater proportion of the NaHCO 3 , and nearly all of the nutrients in the ultrafiltrate. The proximal tubule is also the site of active solute secretion, hormone production, and many of the metabolic functions of the kidney. This review discusses the transport of NaCl, NaHCO 3 , glucose, amino acids, and two clinically important anions, citrate and phosphate. NaCl and the accompanying water are reabsorbed in an isotonic fashion. The energy that drives this process is generated largely by the basolateral Na 1 /K 1 -ATPase, which creates an inward negative membrane potential and Na 1 -gradient. Various Na 1 -dependent countertransporters and cotransporters use the energy of this gradient to promote the uptake of HCO 3 2 and various solutes, respectively. A Na 1 -dependent cotransporter mediates the movement of HCO 3 2 across the basolateral membrane, whereas various Na 1 -independent passive transporters accomplish the export of various other solutes. To illustrate its homeostatic feat, the proximal tubule alters its metabolism and transport properties in response to metabolic acidosis. The uptake and catabolism of glutamine and citrate are increased during acidosis, whereas the recovery of phosphate from the ultrafiltrate is decreased. The increased catabolism of glutamine results in increased ammoniagenesis and gluconeogenesis. Excretion of the resulting ammonium ions facilitates the excretion of acid, whereas the combined pathways accomplish the net production of HCO 3 2 ions that are added to the plasma to partially restore acid-base balance.

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“…Further responses include a prompt acidification of the urine that results from an acute activation of NHE3, the apical Na ϩ /H ϩ exchanger (30). This process facilitates the rapid removal of cellular ammonium ions (39) and ensures that the bulk of the ammonium ions generated in the proximal tubule is excreted in the urine. Finally, a pH-induced activation of ␣-ketoglutarate dehydrogenase reduces the intracellular concentrations of ␣-ketoglutarate and glutamate (29).…”

mentioning

confidence: 99%

Proteomic analysis of the adaptive response of rat renal proximal tubules to metabolic acidosis

Curthoys¹,

Taylor²,

Hoffert³

et al. 2007

American Journal of Physiology-Renal Physiology

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Curthoys NP, Taylor L, Hoffert JD, Knepper MA. Proteomic analysis of the adaptive response of rat renal proximal tubules to metabolic acidosis. Am J Physiol Renal Physiol 292: F140 -F147, 2007. First published August 8, 2006; doi:10.1152/ajprenal.00217.2006.-Proximal tubules were isolated from control and acidotic rats by collagenase digestion and Percoll density gradient centrifugation. Western blot analysis indicated that the tubules were ϳ95% pure. The samples were analyzed by two-dimensional difference gel electrophoresis (DIGE) and DeCyder software was used to quantify the temporal changes in proteins that exhibit enhanced or reduced expression. The mass-to-charge ratios and the amino acid sequences of the recovered tryptic peptides were determined by MALDI-TOF/TOF mass spectrometry and the proteins were identified using Mascot software. This analysis confirmed the well-characterized adaptive responses in glutaminase (GA), glutamate dehydrogenase (GDH), and phosphoenolpyruvate carboxykinase (PEPCK). This approach also identified 17 previously unrecognized proteins that are increased with ratios of 1.5 to 5.6 and 16 proteins that are decreased with ratios of 0.67 to 0.03 when tubules from 7-day acidotic vs. control rats were compared. Some of these changes were confirmed by Western blot analysis. Temporal studies identified proteins that were induced either with rapid kinetics similar to PEPCK or with more gradual profiles similar to GA and GDH. All of the mRNAs that encode the latter proteins contain an AU sequence that is homologous to the pH response element found in GA mRNA. Thus selective mRNA stabilization may be a predominant mechanism by which protein expression is increased in response to acidosis. difference gel electrophoresis; mass spectrometry; phosphoenolpyruvate carboxykinase; glutaminase; mRNA stabilization METABOLIC ACIDOSIS IS A COMMON clinical condition that is caused by the overproduction of an acid or the reduced recovery of bicarbonate and is characterized by a decrease in blood pH and bicarbonate concentration (37). In response to acidosis, the kidneys exhibit a complex set of adaptive responses. Within the renal proximal tubule, this process is characterized by a rapid increase in the catabolism of plasma glutamine (40). Within 1 to 3 h, the arterial plasma glutamine concentration is increased twofold (19) and significant renal extraction becomes evident. Net extraction rapidly reaches 30% of the plasma glutamine, a level that exceeds the percentage filtered by the glomeruli. Thus both apical and basolateral transport of glutamine must contribute to uptake by the epithelial cells of the proximal tubule. In addition, mitochondrial transport and catabolism of glutamine are acutely activated (34). The resulting increases in renal synthesis of ammonium and bicarbonate ions partially restore acid-base balance (4). Further responses include a prompt acidification of the urine that results from an acute activation of NHE3, the apical Na ϩ /H ϩ exchanger (30). This process facilitates the rap...

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Ammoniagenesis by the Isolated Perfused Rat Kidney: The Critical Role of Urinary Acidification

Cited by 42 publications

References 26 publications

Renal ammoniagenesis in an early stage of metabolic acidosis in man.

Renal ammoniagenesis in an early stage of metabolic acidosis in man.

Proximal Tubule Function and Response to Acidosis

Proteomic analysis of the adaptive response of rat renal proximal tubules to metabolic acidosis

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