Ammonia transport by early and late proximal convoluted tubule of the rat.

Good, David W.; DuBose, Thomas D.

doi:10.1172/jci112871

Cited by 34 publications

(12 citation statements)

References 30 publications

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“…The late proximal tubule reabsorbs ammonia in normal animals (7) and can metabolize ammonia to glutamine in an enzymatic reaction catalyzed by glutamine synthetase in which NH 4 ϩ reacts with glutamate to form glutamine. Metabolic acidosis reverses late proximal tubule net ammonia transport from reabsorption to secretion (7) and decreases mouse renal glutamine synthetase expression (4, 16, and current study). In the rat kidney, metabolic acidosis decreases glutamine synthetase activity (5,18), although it does not alter glutamine synthetase protein expression (35).…”

Section: Discussionsupporting

confidence: 52%

Role of the Rhesus glycoprotein, Rh B glycoprotein, in renal ammonia excretion

Bishop

Verlander

Lee

et al. 2010

American Journal of Physiology-Renal Physiology

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Rh B glycoprotein (Rhbg) is a member of the Rh glycoprotein family of ammonia transporters. In the current study, we examine Rhbg's role in basal and acidosis-stimulated acid-base homeostasis. Metabolic acidosis induced by HCl administration increased Rhbg expression in both the cortex and outer medulla. To test the functional significance of increased Rhbg expression, we used a Cre-loxP approach to generate mice with intercalated cell-specific Rhbg knockout (IC-Rhbg-KO). On normal diet, intercalated cell-specific Rhbg deletion did not alter urine ammonia excretion, pH, or titratable acid excretion significantly, but it did decrease glutamine synthetase expression in the outer medulla significantly. After metabolic acidosis was induced, urinary ammonia excretion was significantly less in IC-Rhbg-KO than in control (C) mice on days 2-4 of acid loading, but not on day 5. Urine pH and titratable acid excretion and dietary acid intake did not differ significantly between acid-loaded IC-Rhcg-KO and C mice. In IC-Rhbg-KO mice, acid loading increased connecting segment (CNT) cell and outer medullary collecting duct principal cell Rhbg expression. In both C and IC-Rhbg-KO mice, acid loading decreased glutamine synthetase in both the cortex and outer medulla; the decrease on day 3 was similar in IC-Rhbg-KO and C mice, but on day 5 it was significantly greater in IC-Rhbg-KO than in C mice. We conclude 1) intercalated cell Rhbg contributes to acidosis-stimulated renal ammonia excretion, 2) Rhbg in CNT and principal cells may contribute to renal ammonia excretion, and 3) decreased glutamine synthetase expression may enable normal rates of ammonia excretion under both basal conditions and on day 5 of acid loading in IC-Rhbg-KO mice.

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Section: Discussionsupporting

confidence: 52%

Role of the Rhesus glycoprotein, Rh B glycoprotein, in renal ammonia excretion

Bishop

Verlander

Lee

et al. 2010

American Journal of Physiology-Renal Physiology

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“…The majority of renal ammoniagenesis occurs in the proximal convoluted tubule 20 21 and is dependent on the concentration and activity of glutaminase, the concentration of glutamine reaching the proximal renal tubular cells, and luminal flow rate. 22 Transport of ammonia into the tubular fluid occurs as both NH 4 + (by substitution of the hydrogen ion by the ammonium ion on the Na + -H + antiporter) as well as diffusion of ammonia (NH 3 ) across the cell membrane of the tubular cell into the acidic luminal fluid where it is trapped as NH 4 + ("diffusion trapping"). Ammonia reaching the thick ascending limb of the loop of Henle is actively absorbed into the medullary interstitium by replacement of K + with NH 4 + on the Na-K-2Cl transporter.…”

Section: Discussionmentioning

confidence: 99%

Enhanced renal ammonia excretion following volume expansion in patients with well compensated cirrhosis of the liver

Jalan

Kapoor²

2003

Gut

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Background and aims:In patients with cirrhosis, hepatic encephalopathy is often precipitated by dehydration. This study tests the hypothesis that volume expansion in cirrhotic patients increases renal ammonia excretion. Patients and methods: Sixteen well compensated cirrhotic patients (mean Pugh score 6.7 (SEM 0.4)) were studied after an overnight fast. One litre of 0.9% saline was administered to patients intravenously over one hour. Plasma and urinary ammonia and sodium, renal plasma flow (RPF), glomerular filtration rate (GFR), plasma renin activity (PRA), and angiotensin II (ANG II) were measured before, during, and two hours after saline infusion. Results: Saline infusion resulted in a significant reduction in plasma ammonia (93 (SEM 7) to 56 (4) µmol/l; p<0.05) and RPF and GFR increased (p<0.05). Urinary ammonia excretion increased (p<0.05) significantly. There was a significant reduction in ANG II and PRA (p<0.05 for each) and the change in ammonia excretion correlated directly with the change in urinary sodium excretion (p<0.007), ANG II (p<0.002), and PRA (p<0.01). The mean increase in urinary ammonia excretion during the observation period was 1.08 mmol. Assuming a volume of distribution of 45 litres, the corresponding change in whole body ammonia during the same period was 1.67 mmol. Conclusion:The results of this study suggest that volume expansion reduces plasma ammonia concentration by increasing ammonia excretion and reducing ammoniagenesis.

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“…In keeping with our previous observation [17], volume repletion resulted in an increase in urinary ammonia excretion with consequent decrease in plasma ammonia levels. It is likely that the change in ammonia homoeostasis following volume expansion is probably due to an increase in luminal flow rate mediated by improved renal perfusion [26], the cessation of diuretic therapy [6], which is known to inhibit the transporters involved in the excretion of ammonia, and/or a reduction in renal ammoniagenesis mediated by a decrease in ANG II, which is an important modulator of the ammonia that is synthesized by the proximal tubule [11,[27][28][29][30][31]. In the present study, the significant correlation between a decrease in ANG II and plasma ammonia level on one hand and an increase in urinary ammonia excretion on the other supports this hypothesis, but does not prove unequivocally a cause-effect relationship.…”

Section: Discussionmentioning

confidence: 99%

Reversal of diuretic-induced hepatic encephalopathy with infusion of albumin but not colloid

Jalan

Kapoor

2004

Clinical Science

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In patients with cirrhosis, dehydration induced by diuretics is a common precipitant of hepatic encephalopathy (HE), which may respond to volume expansion. The mechanism of HE in this situation is not fully understood. The present study evaluates the effect of plasma volume expansion on the severity of HE, plasma and urinary ammonia in patients with diuretic-induced HE. Fifteen patients with alcoholic cirrhosis and diuretic-induced HE of Grade 2 or more were enrolled. In eight patients, 4.5% human albumin solution (HAS) was used for volume expansion and in seven patients colloid (Gelofusine) was used. Significant improvement of HE Grade was observed at 24 h and was sustained at 72 h ( P <0.05) only in the group treated with HAS. There were similar and statistically significant reductions in plasma ammonia concentration, plasma renin activity and angiotensin II and an increase in mean arterial pressure, renal plasma flow and urinary ammonia excretion in both groups. Plasma malondialdehyde was elevated in both groups, but was reduced significantly only in the group treated with HAS. The findings of the present study show that plasma volume expansion results in significant reduction in plasma ammonia concentration, possibly through an increase in urinary ammonia excretion. This reduction in ammonia concentration translates into an improvement in mental state only in those patients treated with HAS in whom concomitant reduction in oxidative stress was observed. These data support the notion that other factors, such as oxidative stress, act as adjuncts to ammonia in the pathogenesis of diuretic-induced HE and suggest a possible role for albumin infusion in its treatment.

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Ammonia transport by early and late proximal convoluted tubule of the rat.

Cited by 34 publications

References 30 publications

Role of the Rhesus glycoprotein, Rh B glycoprotein, in renal ammonia excretion

Role of the Rhesus glycoprotein, Rh B glycoprotein, in renal ammonia excretion

Enhanced renal ammonia excretion following volume expansion in patients with well compensated cirrhosis of the liver

Reversal of diuretic-induced hepatic encephalopathy with infusion of albumin but not colloid

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