Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies we suggested that urinary tract obstruction and chronic administration of lithium or amiloride were models of "voltage-dependent" distal renal tubular acidosis (DRTA). Subsequently, differences among these three models suggested that the pathogenesis was far more complex than we originally proposed. A recent study showed that H-adenosinetriphosphatase (H-ATPase) activity was decreased in all three experimental models. In the current experiments we examined the effect of 24-h unilateral ureteral obstruction (UUO) and chronic administration of amiloride and lithium on collecting tubule H-K-ATPase, the other renal H-ATPase enzyme. In the obstructed kidney, cortical collecting tubule (CCT) H-K-ATPase activity was enhanced by 73 +/- 10.0%, whereas the enzyme activity in medullary collecting tubule (MCT) was decreased by 67 +/- 5.4%. In the normal contralateral kidney, activities of H-ATPase, H-K-ATPase, and Na-K-ATPase were increased by approximately 30% in both CCT and MCT. Following amiloride (3 mg.kg-1.day-1 x 3 days ip), rats had normal acid-base status, slight hyperkalemia, and markedly elevated plasma aldosterone levels. Both CCT and MCT H-K-ATPase activities in amiloride-treated rats were unchanged. After LiCl (4 meq.kg-1.day-1 x 3 days ip), rats developed mild metabolic acidosis and had normokalemia and normal aldosterone status. CCT H-K-ATPase activity in lithium-treated rats was decreased by 64 +/- 8.8%, whereas the enzyme activity in MCT remained unchanged. Lithium in vitro (30 meq/l) inhibited CCT, but not MCT, H-K-ATPase activity, whereas amiloride had no effect on the enzyme activity. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:H-K-ATPase in distal renal tubular acidosis: urinary tract obstruction, lithium, and amiloride. 828 19

Urinary obstruction markedly reduces collecting duct Na+ reabsorption. To define the cellular mechanisms of this derangement in Na+ reabsorption in inner medullary collecting duct (IMCD) of obstructed kidneys, suspensions of intact IMCD cells and inner medulla plasma membranes (IMPM) were prepared from 24 h obstructed and untreated control kidneys. Oxygen consumption (QO2) studies revealed marked reductions in both amiloride-sensitive and ouabain-sensitive QO2 but not ouabain-insensitive QO2 in intact IMCD cells from obstructed, compared with control animals, indicating a reduction in oxygen-dependent transport activities of both the Na+ channel and the Na(+)-K(+)-adenosinetriphosphatase (ATPase). Amiloride-sensitive conductive 22Na+ uptake in intact IMCD cells from obstructed kidneys was significantly decreased by 45% at 10 s, 30 s, and 1-5 min (10 s: 2.42 +/- 0.63 vs. 4.49 +/- 0.64 nmol Na+ flux/mg protein, n = 7, P < 0.05; 1 min: 4.65 +/- 0.7 vs. 8.27 +/- 0.98 nmol Na+ flux/mg protein, n = 7, P < 0.05), indicating decreased activity of amiloride-sensitive Na+ channels in these cells. However, immunoblots of IMPM with antibodies to Na+ channel proteins did not show significant differences in content of Na+ channel proteins between membranes from obstructed and control groups. Ouabain-sensitive Na(+)-K(+)-ATPase activity in IMPM of obstructed kidneys was also reduced (61.1 +/- 18.1 vs. 152.6 +/- 25.8 nmol ATP degradation.min-1.mg protein-1, n = 6, P < 0.02), and immunoblots with monoclonal antibodies against the alpha 1- and beta-subunits of rabbit Na(+)-K(+)-ATPase showed a 51 +/- 7% reduction of both subunits in IMPM from obstructed kidneys (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transport defects of rabbit inner medullary collecting duct cells in obstructive nephropathy. 838 52

Urinary tract obstruction impairs urinary concentrating capacity and reabsorption of sodium. To clarify the molecular mechanisms of these defects, expression levels of renal sodium transporters were examined in rats with 24-h bilateral ureteral obstruction (BUO) or at day 3 or 14 after release of BUO (BUO-R). BUO resulted in downregulation of type 3 Na+/H+ exchanger (NHE3) to 41 +/- 14%, type 2 Na-Pi cotransporter (NaPi-2) to 26 +/- 6%, Na-K-ATPase to 67 +/- 8%, type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) to 20 +/- 7%, and thiazide-sensitive cotransporter (TSC) to 37 +/- 9%. Immunocytochemistry confirmed downregulation of NHE3, NaPi-2, Na-K-ATPase, BSC-1, and TSC. Consistent with this downregulation, BUO-R was associated with polyuria, reduced urinary osmolality, and increased urinary sodium and phosphate excretion. BUO-R for 3 days caused a persistant downregulation of NHE3 to 53 +/- 10%, NaPi-2 to 57 +/- 9%, Na-K-ATPase to 62 +/- 8%, BSC-1 to 50 +/- 12%, and TSC to 56 +/- 16%, which was associated with a marked reduction in the net renal reabsorption of sodium (616 +/- 54 vs. 944 +/- 24 micromol x min-1 x kg-1; P < 0.05) and phosphate (6.3 +/- 0.9 vs. 13.1 +/- 0.4 micromol x min-1. kg-1; P < 0.05) demonstrating a defect in renal sodium and phosphate reabsorption capacity. Moreover, downregulation of Na-K-ATPase and TSC persisted in BUO-R for 14 days, whereas NHE3, NaPi-2, and BSC-1 were normalized to control levels. In conclusion, downregulation of renal Na transporters in rats with BUO and release of BUO are likely to contribute to the associated urinary concentrating defect, increased urinary sodium excretion, and postobstructive polyuria.
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PMID:Altered expression of major renal Na transporters in rats with bilateral ureteral obstruction and release of obstruction. 1286 55

Urinary tract obstruction is an important cause of acute renal failure. Several abnormalities in renal tubular function may occur in obstructive nephropathy. The tubular secretion of organic anions is an important function of the kidney that eliminates potentially toxic organic anions from the body, however, the mechanisms involved in organic anions renal elimination in rats with bilateral ureteral obstruction (BUO) have not been elucidated. In this study, it was evaluated the renal handling of p-aminohippurate (PAH) in adult male Wistar rats with BUO. A diminished renal clearance of PAH was observed in BUO rats as consequence of a diminution in the secreted load of this organic anion. The increase in the abundance of organic anions transporter 1 (OAT1) and the absence of modification in cortical renal blood flow, measured with fluorescence microspheres, do not explain the altered secretion of PAH. The diminished Na,K-ATPase activity in cortex from obstructed kidneys might condition OAT1 function. Additionally, it is also possible to conclude that in the presence of BUO, PAH clearance is not a good estimate of renal plasma flow.
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PMID:Renal elimination of organic anions in rats with bilateral ureteral obstruction. 1506 70

The purpose of this study was to evaluate the effects of the anti-inflammatory hormone alpha-melanocyte-stimulating hormone (alpha-MSH) treatment on renal function and expression of aquaporins (AQPs) and Na-K-ATPase in the kidney in response to 24 h of bilateral ureteral obstruction (BUO) or release of BUO (BUO-R). In rats with 24-h BUO, immunoblotting revealed that downregulation of AQP2 and AQP3 was attenuated (AQP2: 38 +/- 5 vs. 13 +/- 4%; AQP3: 44 +/- 3 vs. 19 +/- 4% of sham levels; P < 0.05), whereas downregulation of Na-K-ATPase was prevented by alpha-MSH treatment (Na-K-ATPase: 94 +/- 7 vs. 35 +/- 5% of sham levels; P < 0.05). Immunocytochemistry confirmed the changes in AQP1 and Na-K-ATPase expression. Renal tubular cell apoptosis was confirmed in BUO kidneys, and alpha-MSH treatment virtually completely abolished apoptosis. Furthermore, we measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Forty-eight hours after BUO-R demonstrated that alpha-MSH treatment almost completely prevented the decrease in GFR (nontreated: 271 +/- 50; alpha-MSH: 706 +/- 85; sham: 841 +/- 105 microl x min(-1).100 g body wt(-1), P < 0.05) and ERPF (nontreated: 1,139 +/- 217; alpha-MSH: 2,598 +/- 129; sham: 2,633 +/- 457 microl x min(-1).100 g body wt(-1), P < 0.05). alpha-MSH treatment also partly prevented the downregulation of AQP1 and Na-K-ATPase expression in rats after BUO-R for 48 h. In conclusion, alpha-MSH treatment significantly prevents impairment in renal function and also prevents downregulation of AQP2, AQP3, and Na-K-ATPase during BUO or AQP1 and Na-K-ATPase after BUO-R, demonstrating a marked renoprotective effect of alpha-MSH treatment in conditions with urinary tract obstruction.
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PMID:alpha-MSH prevents impairment in renal function and dysregulation of AQPs and Na-K-ATPase in rats with bilateral ureteral obstruction. 1618 88

Urinary tract obstruction impairs renal function and is often associated with a urinary acidification defect caused by diminished net H+ secretion and/or HCO3- reabsorption. To identify the molecular mechanisms of these defects, protein expression of key acid-base transporters were examined along the renal nephron and collecting duct of kidneys from rats subjected to 24-h bilateral ureteral obstruction (BUO), 4 days after release of BUO (BUO-R), or BUO-R rats with experimentally induced metabolic acidosis (BUO-A). Semiquantitative immunoblotting revealed that BUO caused a significant reduction in the expression of the type 3 Na+/H+ exchanger (NHE3) in the cortex (21 +/- 4%), electrogenic Na+/HCO3- cotransporter (NBC1; 71 +/- 5%), type 1 bumetanide-sensitive Na+-K+-2Cl- cotransporter (NKCC2; 3 +/- 1%), electroneutral Na+/HCO3- cotransporter (NBCn1; 46 +/- 7%), and anion exchanger (pendrin; 87 +/- 2%). The expression of H+-ATPase increased in the inner medullary collecting duct (152 +/- 13%). These changes were confirmed by immunocytochemistry. In BUO-R rats, there was a persistent downregulation of all the acid-base transporters including H+-ATPase. Two days of NH4Cl loading reduced plasma pH and HCO3- levels in BUO-A rats. The results demonstrate that the expression of multiple renal acid-base transporters are markedly altered in response to BUO, which may be responsible for development of metabolic acidosis and contribute to the urinary acidification defect after release of the obstruction.
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PMID:Ureter obstruction alters expression of renal acid-base transport proteins in rat kidney. 1850 79