Renal handling of α-ketoglutarate by the dog

Balagura, Sulamita; Pitts, Robert F.

doi:10.1152/ajplegacy.1964.207.2.483

Cited by 15 publications

(5 citation statements)

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“…This study also reports the effect of NBCe1-A deletion on the intrarenal signaling molecule, 2-oxoglutarate. 2-Oxoglutarate excretion decreases in response to metabolic acidosis (3). The present study shows, for the first time to our knowledge, that 2-oxoglutarate excretion is also regulated in response to hypokalemia.…”

Section: F415supporting

confidence: 66%

NBCe1-A is required for the renal ammonia and K⁺response to hypokalemia

Lee

Harris

Romero

et al. 2020

American Journal of Physiology-Renal Physiology

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Hypokalemia increases ammonia excretion and decreases K+ excretion. The present study examined the role of the proximal tubule protein NBCe1-A in these responses. We studied mice with Na+-bicarbonate cotransporter electrogenic, isoform 1, splice variant A (NBCe1-A) deletion [knockout (KO) mice] and their wild-type (WT) littermates were provided either K+ control or K+-free diet. We also used tissue sections to determine the effect of extracellular ammonia on NaCl cotransporter (NCC) phosphorylation. The K+-free diet significantly increased proximal tubule NBCe1-A and ammonia excretion in WT mice, and NBCe1-A deletion blunted the ammonia excretion response. NBCe1-A deletion inhibited the ammoniagenic/ammonia recycling enzyme response in the cortical proximal tubule (PT), where NBCe1-A is present in WT mice. In the outer medulla, where NBCe1-A is not present, the PT ammonia metabolism response was accentuated by NBCe1-A deletion. KO mice developed more severe hypokalemia and had greater urinary K+ excretion during the K+-free diet than did WT mice. This was associated with blunting of the hypokalemia-induced change in NCC phosphorylation. NBCe1-A KO mice have systemic metabolic acidosis, but experimentally induced metabolic acidosis did not alter NCC phosphorylation. Although KO mice have impaired ammonia metabolism, experiments in tissue sections showed that lack of ammonia does impair NCC phosphorylation. Finally, urinary aldosterone was greater in KO mice than in WT mice, but neither expression of epithelial Na+ channel α-, β-, and γ-subunits nor of H+-K+-ATPase α1- or α2-subunits correlated with changes in urinary K+. We conclude that NBCe1-A is critical for the effect of diet-induced hypokalemia to increase cortical proximal tubule ammonia generation and for the expected decrease in urinary K+ excretion.

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Section: F415supporting

confidence: 66%

NBCe1-A is required for the renal ammonia and K⁺response to hypokalemia

Lee

Harris

Romero

et al. 2020

American Journal of Physiology-Renal Physiology

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“…Based on their pKa, the alkaline urine may deprotonate alpha-ketoglutarate 1- , malonate 1− , and citrate 2− to form alpha-ketoglutarate 2− , malonate 2− , and citrate 3− , respectively, and affect their reabsorption [36,37]. In metabolic/respiratory alkalosis, alpha-ketoglutarate excretion increases to levels that are several times above normal [38,39,40]. Under alkaline loading conditions, the blood concentration of alpha-ketoglutarate rises and net alpha-ketoglutarate reabsorption in the proximal tubule and Henle’s loop is decreased, making the alpha-ketoglutarate secretion increase in the same nephron segments, and leading to a significant increase in the urinary excretion of alpha-ketoglutarate [41,42].…”

Section: Discussionmentioning

confidence: 99%

Monosodium Glutamate (MSG) Renders Alkalinizing Properties and Its Urinary Metabolic Markers of MSG Consumption in Rats

Nahok

Phetcharaburanin

et al. 2019

Biomolecules

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Monosodium glutamate (MSG) is widely used as a flavor enhancer and its effects on human health are still debated. We aimed to investigate whether MSG can act as alkalinizing agent in murine models and if its metabolites are biomarkers of MSG consumption. For this purpose, adult male Wistar rats were given water added with 1 g% MSG or three types of control water, including sodium chloride (NaCl) and sodium bicarbonate (NaHCO3). At 14 days, urinary pH, electrolytes, urinary metabolites and ion-exchanger gene expression were determined. The results revealed that MSG-treated rats had significantly more alkaline urine and higher levels of urinary sodium and bicarbonate similar to NaHCO3 controls. These changes correlated with a lower expression of ion-exchanger genes, namely, CAII, NBC1, and AE1, which are involved in bicarbonate kidney reabsorption. The urinary metabolic profiles also revealed similar patterns for the MSG and NaHCO3 groups. In conclusion, MSG exhibits similar properties to NaHCO3, an alkalinizing agent, with regard to inducing alkaline urine, reducing bicarbonate kidney reabsorption, and generating a specific urinary metabolic pattern. We believe that these observations will be useful to further study the MSG effects in humans.

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“…Tubular reabsorption is active, i.e. against the electrochemical gradient at least in the dog (Cohen & Wittman, 1963;Balagura & Pitts, 1964), and this can occur actively from blood or tubular fluid. Net tubular secretion, which can also occur, is, however, passive and Pitts (1968) favours the view that there are two pumps, one on the luminal membrane, the other on the peritubular membrane; both pump c-oxoglutarate actively into the cells but it can diffuse back through either membrane.…”

Section: Discussionmentioning

confidence: 99%