Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

1. Hypertension is a complication of autologous bone marrow transplantation when therapy includes multiple alkylating agents. We have sought to identify the factors underlying this hypertension. We measured weight, serum creatinine, plasma renin activity, aldosterone and digoxin-like immunoreactive factor (DLIF), by digoxin radioimmunoassay, in 18 patients. Plasma catecholamines were also measured in five patients. 2. Of the 18 patients studied, 15 became hypertensive. The variable most consistently associated with these individuals' hypertension was DLIF activity which was increased in 14 of the 15 hypertensive patients (P = 0.055, Fisher exact test). Serum creatinine was increased at some point in seven of the 15 hypertensive patients, weight was increased in five and plasma renin activity and aldosterone were increased in one. Catecholamines were not increased in any of the five patients in which they were measured. 3. The association between changes in mean arterial pressure (MAP) and changes in DLIF for the group as a whole was assessed by analysing one data pair per patient, representing the maximal MAP. This correlation was significant (r = 0.75, P = 0.001). 4. Within individual patients, changes in MAP and changes in serum DLIF concentrations were significantly correlated (r greater than 0.50, P less than 0.05) in six of 15 hypertensive patients. 5. Digitalis-like factor (DLF) was measured by inhibition of (Na+,K+)-adenosine 5'-triphosphatase in five patients and DLF and DLIF were significantly correlated (r = 0.081, P = 0.0001). DLF and MAP were also significantly correlated (r = 0.59, P = 0.002). 6. This represents the first longitudinal study of the relationship between DLIF and blood pressure in hypertensive individuals, and the results suggest that DLIF may contribute to the increased blood pressure in some of these subjects.
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PMID:Endogenous digoxin-like immunoreactive factor and digitalis-like factor associated with the hypertension of patients receiving multiple alkylating agents as part of autologous bone marrow transplantation. 255 6

The present study aimed to elucidate the role of Na, K-ATPase inhibitor in renal sodium metabolism in essential hypertension. Mean arterial pressure (MAP), heart rate(HR), urine volume (UV), urinary excretion of sodium (UNaV), endogenous creatinine clearance (Ccr), fractional excretion of sodium (FENa), plasma renin activity(PRA) plasma aldosterone concentration(PAC), plasma noradrenaline concentration (PNA) and urinary excretion of noradrenaline(UNA) were measured before and after intravenous injection of ouabain (0.1 mg/m2.BSA) in 12 normotensive(NT) and 22 mild-to-moderate essential hypertensive subjects(EHT). Following ouabain injection, UV, UNaV FENa significantly increased, but PRA decreased, in both NT and EHT. MAP, HR, Ccr, PNA, and UNA did not change significantly in either group. On the other hand, a significant decrease in PAC was observed in NT, but not in EHT. The changes of UNaV and FENa were significantly attenuated in EHT as compared to NT. No significant difference in change of MAP, HR, UV, Ccr, PNA, UNA, or PRA was demonstrated between NT and EHT. A significantly positive correlation was found between delta UNaV and delta FENa in both NT and EHT, while no significant correlation was observed between delta UNaV and delta MAP, delta UV, delta Ccr, delta PRA, delta PAC, delta PNA and delta UNA in either group. These results suggest that 1) Na, K-ATPase inhibitor clearly augments natriuresis by suppression of sodium reabsorption in renal tubules, 2) since this augmentation was attenuated, there is an elevation of endogenous Na, K-ATPase inhibitor(s) should be considered in EHT, and 3) an increase of the inhibitor might participate to the hypertensive mechanism in EHT.
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PMID:[The role of the Na, K-ATPase inhibitor in renal sodium handling in patients with essential hypertension]. 255 14

Gentamicin nephrotoxicity increases renal cortex calcium and sodium and decreases renal cortex Na-K-ATPase activity. Human acute renal failure is accompanied by an increase in parathyroid hormone (PTH), a hormone that stimulates calcium uptake by tissues, and by a decrease in thyroid hormone, a hormone that increases renal cortex Na-K-ATPase activity. This study evaluated the role of extracellular calcium, PTH, and thyroxine in the pathogenesis of gentamicin nephrotoxicity. Chronically parathyroidectomized hypocalcemic rats (PTXG) given gentamicin (30 mg/kg s.c. twice daily for 8 days) were not protected from renal failure when compared with intact rats given gentamicin (NG), serum creatinine being 4.4 +/- 1.0 and 3.7 +/- 0.7 mg/dl, respectively, compared with normals (N), 1.2 +/- 0.1 mg/dl. Rats given thyroxine (10 micrograms/100 g body wt for 10 days) before and during gentamicin (PTXT4G) had a serum creatinine not significantly different from normals, 2.1 +/- 0.4 mg/dl. Plasma T4 was reduced in PTXG, NG, and PTXT4G compared with N, but the value for PTXT4G was significantly higher than for either PTXG or NG. Renal cortex Na-K-ATPase activity (mumol Pi X mg prot-1 X h-1) was lower in PTXG (2.3 +/- 0.2) and NG (2.4 +/- 0.5) compared with N (3.7 +/- 0.1), but activity was not reduced in PTXT4G (3.2 +/- 0.2) Thyroxine was protective also against gentamicin nephrotoxicity in intact rats. Clearance and excretion studies indicated that this protection did not result from an increase in glomerular filtration rate, filtered load of calcium, or urinary calcium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of thyroxine but not parathyroidectomy on gentamicin nephrotoxicity. 257 82

Biochemical mechanisms underlying cyclosporine (CsA)-induced nephrotoxicity and the effect of concomitant administration of prednisolone (Pr) on the nephrotoxicity were studied. Male Wistar rats were treated with the vehicles used for CsA and Pr administration (group 1), Pr alone (group 2), CsA alone (group 3), or CsA plus Pr (group 4), respectively. The dose of CsA was 5 mg/kg/day, i.p. for the initial 7 days, and was decreased to 2.5 mg/kg/day i.p. thereafter. The dose of Pr was always maintained at one-tenth of that of CsA. At 10, 30, and 90 days after the initiation of these treatments, blood urea nitrogen (BUN) and serum levels of creatinine and CsA were determined. The syntheses of DNA, RNA, and protein, Na+, K+-adenosine triphosphate (ATP)ase activity, and ATP content were measured using homogenates of the renal cortex obtained from each experimental group. At an early stage (at 10 and 30 days) of CsA administration, the impairment of renal function and inhibition of the synthesis of DNA and RNA appeared in groups 3 and 4. The magnitude of these changes was found to be greater in group 3 (CsA alone) than in group 4 (CsA plus Pr). Group 3 also showed a significant reduction of Na+, K+-ATPase activity as well as ultrastructural abnormalities. At a later stage (at 90 days), however, such differences in nephrotoxicity between groups 3 and 4 were not detected. These results strongly suggest that inhibition of the synthesis of DNA and RNA and the activity of enzymes related to the functions of cell membrane, such as Na+, K+-ATPase, may be involved in the occurrence of CsA-induced nephrotoxicity. The present results also suggest that the concomitant administration of Pr with CsA may reduce the nephrotoxicity of CsA at early stages of CsA administration, but this preventive effect of Pr may disappear if the administration of CsA is prolonged.
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PMID:Biochemical mechanisms underlying cyclosporine-induced nephrotoxicity. Effect of concomitant administration of prednisolone. 282 92

1. The effects of jaundice on renal and circulatory function were investigated in chronic bile duct ligated (CBDL) rats 6 days after surgery. Sham operated (SO) animals served as controls. 2. Body weight was significantly reduced, whereas blood pressure remained unaltered, 6 days after bile duct ligation when serum bilirubin had risen to 169 +/- 18 (SEM) as compared with 2.8 +/- 0.3 mumol/l in SO rats. When compared with control values before surgery, urinary volume had significantly increased and absolute excretion of sodium, potassium, chloride and phosphate had decreased on day 6 after CBDL. Endogenous creatinine clearance was markedly depressed when compared with SO rats. Whereas fractional excretion of potassium remained unaltered, fractional excretion of sodium and of phosphate was significantly increased. 3. Except for a significant increase in urinary thromboxane B2 (TXB2) excretion in CBDL rats, no significant changes were observed in urinary excretion of prostaglandin (PG) E2, in the synthesis of PGE2, 6-keto-PGF1 alpha and TXB2 by isolated aortic tissue in vitro, nor in renal and cardiac adenosine triphosphatase activities or renal cortical mitochondrial function. 4. The adenosine triphosphate content of kidney cortex and cardiac mitochondrial function were significantly depressed in CBDL rats. 5. The results demonstrate that jaundice in CBDL rats is associated with functional and metabolic disturbances of the kidney and cardiac muscle, which may contribute to the renal and haemodynamic characteristics observed in jaundiced animals and humans.
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PMID:The kidney and cardiovascular system in obstructive jaundice: functional and metabolic studies in conscious rats. 282 70

We compared 86rubidium by erythrocytes of preterm infants and adults as a measurement of their Na+, K+, ATPase enzyme system. In neonates, total uptake (0.92 +/- 0.13 micrograms/10(6) cells) and specific uptake (0.64 +/- 0.076 micrograms/10(6) cells) were significantly higher than in adults (0.52 +/- 0.1 and 0.29 +/- 0.06 micrograms/10(6) cells, respectively; p less than 0.025). The percentage of specific uptake from total uptake was higher in infants (73.3 +/- 2.3%) than in adults (57.9 +/- 4.6%) (p less than 0.005). No differences were found in the affinity constant of 86Rb uptake between infants (4.35 +/- 0.48 ng/ml) and adults (4.85 +/- 0.48 ng/ml). Stratification of infants according to their serum K+ concentrations revealed that levels above 5.4 mEq/liter were associated with a higher specific uptake (0.79 +/- 0.107 micrograms/10(6) cells) than in normokalemic infants (0.54 +/- 0.09 micrograms/10(6) cells) or adults (0.304 +/- 0.061 micrograms/10(6) cells) (p less than 0.05). The difference between hyperkalemic and normokalemic infants persisted after excluding those who received adult packed cells (0.88 +/- 0.1 and 0.6 +/- 0.12 micrograms/10(6) cells, respectively) (p less than 0.05). Infants with serum K+ greater than 5.8 mEq/liter received on average significantly more K+ in previous days (2.46 +/- 0.49 versus 1.13 + 0.34 mEq/kg.day; p less than 0.025). The different K+ level could not be attributed to different creatinine clearance in the two groups.
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PMID:Comparison of the digitalis receptor in erythrocytes from preterm infants and adults. 283 86

Changes in renal function, Na+-K+-ATPase activity and PAH transport system in kidney cortex were studied in rats treated with cadmium. Subcutaneous injections of CdCl2 (2 mg Cd/kg.day) for 16 days induced a marked polyuria and a hyposthenuria. These changes were accompanied by increase in urinary protein, glucose, urea, calcium, phosphate, chloride and potassium excretions. The change in urine flow was proportional to the change in total osmotic solute excretion. Creatinine excretion and TcH2O remained unchanged. Na+ excretion was not increased, but the Na+-K+-ATPase of renal cortex was significantly inhibited. PAH uptake by renal cortical slices was markedly attenuated in Cd-treated rats. The Vmax for active PAH influx was drastically reduced, but the Km was not changed. The passive influx and efflux of PAH across the basolateral membrane and the renal tissue oxygen consumption were not apparently altered in Cd-treated animals. These results indicate that 1) the nature of Cd-induced polyuria and hyposthenuria is an osmotic diuresis induced by proximal tubular rejection of various substances, and 2) the mechanism of impaired renal PAH excretion in Cd-treated animals is a loss of organic anion carriers in proximal tubular basolateral membranes.
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PMID:Changes in renal function in cadmium-intoxicated rats. 285 38

Studies in rats have shown that fecal potassium excretion and colonic mucosa Na-K-ATPase activity are elevated during dietary potassium loading and in chronic renal insufficiency. We studied Na-K-ATPase activity in human rectal mucosa in normal subjects as well as in patients with chronic renal insufficiency (creatinine clearance 2 to 72 mL/min). In normals, Na-K-ATPase activity was 4.34 +/- 0.83 mumol P/mg protein. After 2 weeks on a potassium intake of 300 mmol/d the mean activity did not differ significantly from the control value (2.49 +/- 1.30). In none of the patients with renal failure was Na-K-ATPase activity beyond the range found in the normal subjects, irrespective of serum potassium; the mean activity was 3.50 +/- 0.85. Like others, however, we found a two-fold increase in Na-K-ATPase activity in potassium loaded rats. Possible explanations for these differences are discussed.
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PMID:Sodium potassium ATPase activity in human rectal mucosa with and without renal insufficiency. 298 40

We have previously shown that a natriuretic factor which is present in a small molecular weight fraction (IV) of serum and urine from salt loaded animals and healthy subjects, respectively, inhibits the Na-K-ATPase enzyme in vitro and also binds to a specific digoxin antibody. In the present study digoxin-like immunoreacting activity (DLIA) was therefore determined in the serum of healthy volunteers during low (35 nmol/day) and high (greater than 400 mmol/day) sodium intake and of patients with chronic renal failure and serum creatinine concentrations ranging from 127 to 757 mumol/l. DLIA was determined with a radioimmunoassay for digoxin in native serum and in the salt (III) and post-salt (IV) serum fractions eluted from a Sephadex G-25 column. DLIA in native serum of healthy subjects was less than 0.125 ng/ml. After gel filtration DLIA eluted exclusively in the small molecular weight salt (F III) and post-salt (F IV) fractions. Whereas DLIA increased in F III and decreased in F IV, total DLIA in F III + IV slightly increased from 0.37 +/- 0.03 to 0.49 +/- 0.05 ng/ml (p less than 0.01) with the change from low to high sodium intake. DLIA in native serum of uremic patients ranged from 0 to 1.70 ng/ml and was detectable consistently only in patients with serum creatinine concentrations above 250 mumol/l. DLIA in F III which averaged 0.22 +/- 0.04 ng/ml and total activity which ranged from 0.11 to 0.88 ng/ml closely correlated with the degree of renal impairment (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation of endogenous digoxin-like immunoreacting activities to salt balance and renal function in man. 298 6

The effects of unilateral nephrectomy and the impact of gentamicin administration on renal tissue enzyme activities in adult Wistar rats were investigated. Gentamicin 200 mg/kg body wt. or an equivalent volume of saline to control rats was administered subcutaneously on three consecutive days, followed by unilateral nephrectomy. Rats were killed on day 3, 7 or 14 following nephrectomy. Alkaline phosphatase, predominantly a proximal tubular brush border enzyme, rose in both the experimental and control groups, however, significantly less in the gentamicin treated rats. Aspartate aminotransferase activity, an enzyme participating in renal glucogenesis, increased transiently in the control but remained unchanged in the experimental group. No difference in glucose-6-phosphate dehydrogenase activity between the two groups was observed, probably reflecting the localization of this enzyme to distal tubular segments, a site unaffected by gentamicin. Significant and similar increases in Mg2+ and Na+ K+ ATPase were observed on day 14 in both groups. The administration of the drug resulted in a marked reduction in oxygen consumption, with a higher oxidation to phosphorylation ratio (P/O). Serum creatinine concentration was significantly higher on days 3 and 7 in the experimental group reverting to control values on the 14th day. Urea concentration increased significantly on days 3 and 7, decreasing on the 14th day to values slightly, but significantly, higher than those of the controls.
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PMID:Changes in renal enzyme activities following the administration of gentamicin to unilateral nephrectomized rats. 300 57


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