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)

The effects of citrinin, ochratoxin A, or a combination of the two mycotoxins on the hepatic monooxygenase system and on hepatic and renal adenosinetriphosphatase (ATPase) activities were examined in neonatal rats exposed to a single treatment of one or both toxins. Animals received (po) 25 mg/kg citrinin, 1 mg/kg ochratoxin A, or 25 mg/kg citrinin plus 1 mg/kg ochratoxin A within 24 h of birth. Pups were killed 12 d later. Citrinin or ochratoxin A alone did not affect hepatic ATPase. Renal oligomycin-sensitive Mg2+-ATPase was inhibited to the same degree by ochratoxin A and the combination treatment. A synergistic effect of the two mycotoxins was observed on renal Na+-K+-ATPase. Significant effects, due to the mycotoxin interaction, were also observed on cytochrome P-450 content, NADPH-dependent dehydrogenase, and NADPH-cytochrome c reductase.
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PMID:Effects of the mycotoxins citrinin and ochratoxin a on hepatic mixed-function oxidase and adenosinetriphosphatase in neonatal rats. 646 Jan 15

1. Lantana intoxication of guinea-pig caused a decrease in hepatic microsomal protein content, the phospholipid: protein ratio, and the cholesterol: protein ratio. 2. Activities of aniline hydroxylase, aminopyrine N-demethylase, NADH-cytochrome c reductase, NADH-ferricyanide reductase, UDP-glucuronosyl transferase, cytochrome P-450 and glucose 6-phosphatase were decreased. 3. Activities of Mg2+ -ATPase and Na+ -K+ -ATPase were increased. However, activities of 5-nucleotides and NADPH-cytochrome c reductase were unaffected. 4. The liver endoplasmic reticulum is an important target organelle during lantana poisoning of guinea-pigs.
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PMID:Biochemical changes in hepatic microsomes of guinea-pig under lantana toxicity. 711 63

Toxicological studies of a leachable stabilizer Di-n-butyltin dilaurate (DBTL) were undertaken. Effects of DBTL after 15 days oral exposure to rats were studied on brain and liver enzyme activities. A significant decrease in body weight gain of DBTL exposed rats were observed. No effect was observed in the activities of brain enzymes, succinic dehydrogenase, adenosine triphosphatase, acetylcholine esterase and monoamine oxidase. In liver, DBTL treatment resulted in a significant decrease in the activities of microsomal enzymes glucose-6-phosphatase, aminopyrine-N-demethylase, benzphetamine-N-demethylase, aniline hydroxylase, benzo(a)pyrene hydroxylase and also on cytochrome P-450 content, whereas no difference in the activities of mitochondrial enzymes, succinic dehydrogenase, Mg2+-adenosine triphosphatase as well as in the activity of lysosomal enzyme acid phosphatase was observed. Duration of exposure dependent increase in pentabarbital induced sleeping time was also observed. DBTL treatment produced an induction in heme oxygenase activity whereas the activity of -aminolevulinic acid synthetase remained unaltered. The results demonstrate that DBTL significantly affects the biotransformation mechanism and heme metabolism of hepatocytes.
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PMID:Toxicological studies of a leachable stabilizer di-n-butyltin dilaurate(DBTL): effects on hepatic drug metabolizing enzyme activities. 726 48

The matrix of peroxisomes has been considered to be homogeneous. However, a fine network of tubules is visible in electron micrographs at very high magnification. This substructure becomes more positive in a high-contrast photocopy and with an imaging-plate method. Clofibrate, bezafibrate, and aspirin increase peroxisomes. In proliferated peroxisomes, the density of matrix is low and the fine network is more visible. The effect of proliferators is more significant in males than in females. This sex difference may involve the action of estrogen, growth hormone, cytochrome P-450 and thyroxine. Mg-ATPase is localized on the limiting membrane of peroxisomes. Even on the membrane of irregular projections of proliferated peroxisomes, Mg-ATPase is evident cytochemically. Carnitine acetyltransferase is detectable in the matrix of proliferated peroxisomes. Withdrawal of proliferators results in a rapid decrease of peroxisomes. This may indicate the existence of peroxisome suppressors. Alternatively, dynamic transformation of vesicular to tubular types in peroxisome reticulum may occur. Such transformation has been described in lysosomes and mitochondria.
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PMID:Molecular organization of hepatocyte peroxisomes. 755 86

This study was designed to assess Cyclosporin A (CsA) nephrotoxicity in the rabbit-possibly a more sensitive species than the rat-and to explore the mechanism of this toxicity with special attention to glutathione metabolism disturbances and cytochrome P-450 level in the kidney. CsA given for three days at a daily dose of 50 mg/kg (s.c.) induced nephrotoxicity as assessed by histological abnormalities and by a significant increase in blood urea nitrogen and urinary enzyme activities: N-acetyl-beta-D-glucosaminidase and L-gamma-glutamyl-transferase. This observed renal injury was of the same order as that obtained in the rat. In addition, there was a significant increase in oxidized glutathione content (40%) while reduced glutathione level remained unchanged. Concurrently, there was a significant decrease in renal cortex glutathione reductase (49%) and to a lesser extent in glutathione peroxidase activities (16%) whereas that of glutathione-S-transferase was not modified. A significant increase in renal cortex cytochrome P-450 (3-fold versus controls) was also observed. The mechanism of CsA nephrotoxicity is to be related to a cytochrome P-450 induction. This event could induce the observed impairments in renal glutathione metabolism and Na+K(+)-ATPase activity, via a possible increase in eicosanoid metabolism.
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PMID:Effects of cyclosporin on kidney glutathione metabolism and cytochrome P-450 in the rabbit: possible implication of eicosanoid metabolism. 782 Dec 32

The medullary thick ascending limb of Henle's loop (mTALH) of the rabbit metabolizes arachidonic acid (AA) via a cytochrome P-450 (P-450) monooxygenase pathway to several products, of which the principal are 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) and 1,20-eicosatetraenedioic acid (20-COOH-AA). To understand their mechanism of action on alkali cation metabolism in mTALH cells, we have compared their effects with those of ouabain and furosemide. Incubation of rabbit isolated mTALH cells with either 1 mM ouabain or furosemide decreased K+ content from a control of 1,015 +/- 51 peq/micrograms protein to 717 +/- 41 and to 548 +/- 48 peq/micrograms protein, respectively, whereas they had opposite effects on Na+ content; from a control of 138 +/- 22 peq/micrograms protein, ouabain increased Na+ content to 357 +/- 37 peq/micrograms protein, and furosemide decreased it to 64 +/- 23 peq/micrograms protein. Preincubation with either 20-HETE (1 microM) or 20-COOH-AA (1 microM) decreased Na+ and K+, resembling furosemide in their effects on Na+ and K+ content. In other experiments we used monensin-treated cells to determine 86Rb uptake under conditions in which Na+ entry into the cell was not rate limiting. Under these conditions ouabain still inhibited 86Rb uptake, and the effect of AA was blocked. A major action of AA metabolites on Na(+)-K(+)-adenosinetriphosphatase was thereby excluded. Furthermore, AA metabolites did not inhibit Ba(2+)-sensitive 86Rb efflux, indicating that they do not act through K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytochrome P-450 arachidonate metabolites affect ion fluxes in rabbit medullary thick ascending limb. 802 7

We have previously shown that parathyroid hormone (PTH)-(1-34) or its analogue PTH-(3-34) inhibits proximal tubule (PT) Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity independently of adenosine 3',5'-cyclic monophosphate generation. The present study used PT suspensions to investigate the signaling pathway responsible for this hormonal action. PTH-(1-34) and PTH-(3-34) significantly increased the release of arachidonic acid (AA) compared with control tubules, suggesting activation of phospholipase A2 (PLA2). AA, 10(-6) M, mimicked the inhibition of the pump by 10(-8) M PTH-(3-34), and together were not additive. Eicosatetraynoic acid, 3 microM, a general inhibitor of AA metabolism, blocked the PTH action. Indomethacin, 10 microM, an inhibitor of AA-dependent cyclooxygenase, did not prevent the PTH action, but 2 microM 7-ethoxyresorufin, a cytochrome P-450 inhibitor, prevented the PTH effect. 20-Hydroxyeicosatetraenoic acid (20-HETE), the main product of P-450 metabolism in PT, inhibited Na(+)-K(+)-ATPase activity to the same extent as 10(-8) M PTH-(3-34), was not additive with PTH, and was maximally inhibitory at 10(-7) M. To further investigate the signaling pathway responsible for PTH-activated PLA2, we tested the effect of PTH on cytoplasmic free Ca2+ ([Ca2+]i). PTH-(1-34), 10(-7) M, did not affect [Ca2+]i, although 10(-8) M angiotensin II promoted a Ca2+ transient. Treatment of PT with pertussis toxin (PTX) did not prevent the PTH action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parathyroid hormone inhibits Na(+)-K(+)-ATPase through a cytochrome P-450 pathway. 816 Aug

Cytochrome P-450 has been proposed to underlie the mechanism of regulation of the plasma membrane Ca2+ permeability by the Ca2+ content of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. We have investigated the effects on divalent cation uptake in rat thymic lymphocytes of three structurally related imidazole reagents reported to inhibit redox mechanisms. Changes in intracellular Ca2+ concentration and intracellular Mn2+ concentration were measured fluorimetrically with indo-1 and/or quin-2. Econazole, miconazole, and SKF 96365 were found to be potent blockers of Ca2+ and Mn2+ uptake activated by release of Ca2+ from intracellular stores induced by thapsigargin. Additionally, we found that concentrations of these agents required to abolish divalent cation uptake also released Ca2+ from the thapsigargin-sensitive intracellular stores, consistent with inhibition of the endosomal Ca(2+)-ATPase. In agreement with this suggestion, we have found that all three of these agents are potent inhibitors of isolated sarcoplasmic reticulum Ca(2+)-ATPase. We conclude that econazole, miconazole, and SKF 96365 inhibit cytochrome P-450-independent filling of intracellular Ca2+ pools, as well as store-regulated Ca2+ entry, and caution against the use of these compounds as selective inhibitors of cytochrome P-450.
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PMID:Inhibition of Ca2+ transport pathways in thymic lymphocytes by econazole, miconazole, and SKF 96365. 838 87

Proton pump inhibitors irreversibly inhibit the enzyme hydrogen-potassium adenosine triphosphatase (H(+)-K(+)-ATPase), which suppresses acid production in the parietal cell of the stomach. Omeprazole, the prototype proton pump inhibitor, has proved to be very effective. However, newer agents are being designed to provide even more potent acid suppression and longer-acting proton pump inhibition, with the goal of further controlling gastric hypersecretion. Lansoprazole is the second proton pump inhibitor available on the market. Pantoprazole is not yet available for general use in the United States. However, each of these drugs is slightly different from omeprazole, thus offering some possible clinical advantages. Compared with omeprazole, lansoprazole has a longer duration of action and improved activity against Helicobacter pylori, while pantoprazole has less interaction with the cytochrome P-450 system and more predictable bioavailability. All three agents have similarly high healing rates for acid peptic diseases and appear to be superior to histamine2-receptor antagonists.
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PMID:Proton pump inhibitors: new drugs and indications. 854 54

The role of cytochrome P-450 in the regulation of plasma membrane Ca+2 permeability of human peripheral T-lymphocytes by intracellular Ca+2 was examined. We assessed the effect of imidazole inhibitors of cytochrome P-450 on the intracytoplasmic free Ca+2 ([Ca+2]i) response generated using the microsomal ATPase inhibitor thapsigargin (THG) to deplete the intracellular Ca+2 stores. Econazole, miconazole and clotrimazole dramatically inhibited the THG mediated increase in [Ca+2]i and induced an increase in [Ca+2]i themselves. This inhibitory effect was previously observed in other cell systems and was attributed to inhibition of cytochrome P-450 by these agents. However, we evaluated a variety of structurally dissimilar P-450 inhibitors and found that none affected [Ca+2]i, indicating that the mechanism of imidazole action does not involve P-450.
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PMID:Modulation of human T-lymphocyte plasma membrane Ca2+ permeability by imidazole antimycotics. 877 69


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