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 enzymatic response to injury appears as an increase in enzymatic activity in the periphery of burns and other injuries. The following processes constitute the enzymatic response: 1) release, 2) activation and 3) synthesis of enzymes. Processes 2) and 3) are dependent upon the fibroblast, which is an activated fibrocyte. Among the fibrocyte activators, and thus among the mediators of the enzymatic response, are histamine, serotonin, kinins, prostaglandins etc. The effects of non-steroidal anti-inflammatory drugs on the enzymatic response to burn injury were studied. Indomethacin, mefenamic acid or aspirin, suspended in carboxymethylcellulose, were given to rats by stomach tube. Controls received carboxymethylcellulose only. Circular burns were inflicted on anaesthetized animals which were killed 30 min, 2 h or 4 h after burning. The burns were studied histologically and enzyme histochemically by using the methods for prostaglandin synthetase, esterases, and adenosine triphosphatase. Aspirin had no effect on the enzymatic response. Mefenamic acid and indomethacin caused a less severe enzymatic response in the 4-h groups as compared to control rats.
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PMID:On the enzymatic response to injury and its mediators. 15 85

Salmonella typhimurium, an organism that invades intestinal mucosa but does not elaborate a traditional enterotoxin, evokes ileal secretion by causing alterations in active sodium and chloride transport mechanisms. To evaluate the possibility that these changes in transport might be related to the adenylate cyclase-cyclic AMP or NA+-K+-adenosine triphosphatase (ATPase) systems, mucosal adenylate cyclase, cAMP phosphodiesterase, Na+-K+ and Mg++ ATPase activities, and cAMP concentrations were measured in rabbit ileal loops infected with two strains of S. typhimurium. Strain TML invades the mucosa and evokes fluid secretion whereas strain SL 1027 invades but does not evoke secretion. Cholera toxin-stimulated loops were also studied. When compared to control loops, TML-infected mucosa demonstrated a marked increase in adenylate cyclase activity, in cAMP concentration, and no change in phosphodiesterase or ATPase activities. SL 1027-infected mucosa demonstrated no change in either adenylate cyclase or ATPase activities. Indomethacin pretreatment of cyclase activation. In contrast, indomethacin pretreatment of cholera toxin exposed animals resulted in only a partial reduction of secretion while not altering the stimulation of adenylate cyclase. These results suggest that: (1) S. typhimurium causes ileal secretion by stimulating adenylate cyclase; (2) mucosal invasion alone (SL 1027) is not sufficient to activate adenylate cyclase, and (3) Na+-K+-ATPase does not appear to be involved in salmonella-induced secretion. The mechanism of salmonella activation of adenylate cyclase is unclear but apparently differs from that of cholera toxin in that it is inhibited by indomethacin. This might be explained by the participation of prostaglandins in the salmonella activation process.
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PMID:Pathogenesis of Salmonella-mediated intestinal fluid secretion. Activation of adenylate cyclase and inhibition by indomethacin. 17 99

1. To further explore the Na(+)-retaining effect of indomethacin along the whole length of the nephron, the Na(+)-K(+)-ATPase activity of isolated tubules from indomethacin-pretreated rats was compared with that of tubules isolated from intact rats and exposed directly to prostaglandin E2. 2. Indomethacin increased Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (+24%, P < 0.001 versus control), proximal straight tubule (+75%, P < 0.001 versus control), medullary thick ascending limb (+68%, P < 0.001 versus control), cortical thick ascending limb (+7%, not significant) and cortical collecting duct (+18%, P < 0.025 versus control). In contrast, in the distal convoluted tubule indomethacin decreased Na(+)-K(+)-ATPase activity by -42% (P < 0.001 versus control). 3. Indomethacin also strongly increased Na(+)-K(+)-ATPase activity in the cortical collecting duct of adrenalectomized rats. 4. In isolated tubules from control rats, prostaglandin E2 reduced Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (-33%, P < 0.05), proximal straight tubule (-60%, P < 0.001), medullary thick ascending limb (-43%, P < 0.001), cortical thick ascending limb (-25%, P < 0.001) and cortical collecting duct (-45%, P < 0.001) and in the distal convoluted tubule, prostaglandin E2 increased Na(+)-K(+)-ATPase activity (+32%, P < 0.05). 5. That these changes in Na(+)-K(+)-ATPase activity in indomethacin-pretreated rats and prostaglandin E2-treated controls are similar in magnitude but occur in opposite directions suggests that the response to indomethacin is mediated by inhibition of prostaglandin E2 synthesis in the nephron. In the cortical collecting duct the effect of indomethacin is aldosterone-independent.
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PMID:Indomethacin and sodium retention in the rat: role of inhibition of prostaglandin E2 synthesis. 132 47

Erythrocytes of diabetic subjects (non-insulin dependent) were found to have eight- to ten-fold higher levels of endogenously formed thiobarbituric acid reactive malonyldialdehyde (MDA), thirteen-fold higher levels of phospholipid-MDA adduct, 15-20% reduced Na(+)-K(+)-ATPase activity with unchanged Ca+2-ATPase activity, as compared with the erythrocytes from normal healthy individuals. Incubation of normal erythrocytes with elevated concentrations (15-35 mM) of glucose, similar to that present in diabetic plasma, led to the increased lipid peroxidation, phospholipid-MDA adduct formation, reduction of Na(+)-K(+)-ATPase (25-50%) and Ca+2-ATPase (50%) activities. 2-doxy-glucose was 80% as effective as glucose in the lipid peroxidation and lipid adduct formation. However, other sugars, such as fructose, galactose, mannose, fucose, glucosamine and 3-O-methylmannoside, and sucrose, tested at a concentration of 35 mM, resulted in reduced (20-30%) lipid peroxidation without the formation of lipid-MDA adduct. Kinetic studies show that reductions in Na(+)-K(+)-ATPase and Ca+2-ATPase activities precede the lipid peroxidation as the enzyme inactivation occur within 30 min of incubation of erythrocytes with high concentration (15-35 mM) of glucose, while lipid peroxidation product, MDA appears at 4 hr and lipid-MDA adducts at 8 hr. The lipoxygenase pathway inhibitors, 5,8,11-eicosatriynoic acid and Baicalein (5,6,7-trihydroxyflavone), reduced the glucose-induced lipid peroxidation by 30% and MDA-lipid adduct formation by 26%. Indomethacin, a cyclooxygenase pathway inhibitor, had no discernible effect on the lipid peroxidation in erythrocytes. However, the inhibitors of lipid peroxidation, 3-phenylpyrazolidone, metyrapone, and the inhibitors of lipoxygenase pathways did not ablate the glucose-induced reduction of Na(+)-K(+)-ATPase and Ca+2-ATPase activities in erythrocytes. Erythrocytes produce 15-HETE (15-hydroxy-eicosatetraenoic acid), which is augmented by glucose. These results suggest that the formation of lipoxygenase metabolites potentiate the glucose-induced lipid peroxidation and that the inactivation of Na(+)-K(+)-ATPase and Ca+2-ATPase occurs as a result of non-covalent interaction of glucose with these enzymes.
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PMID:Glucose induces lipid peroxidation and inactivation of membrane-associated ion-transport enzymes in human erythrocytes in vivo and in vitro. 165 8

Prostacyclin (PGI2) did not alter the basal perfusion pressure in the isolated rat mesenteric arteries perfused with Krebs' solution, but produced a biphasic effect in arteries preconstricted with norepinephrine or arginine vasopressin: constriction, then prolonged dilation. Both these components of PGI2 effect were diminished in arteries denuded of their endothelia by a 10 min perfusion with distilled water or p-bromophenacyl bromide (10 microM). The present study elucidates the mechanism of these PGI2 actions. Indomethacin (0.28 microM) SQ 29548 (1 microM, thromboxane A2 receptor antagonist), saralasin (1 microM, angiotensin II receptor antagonist) or the free radical scavengers, superoxide dismutase (60 U/ml) and catalase (40 U/ml) did not inhibit the initial vasoconstriction, suggesting it was not mediated through endothelially generated thromboxane A2, angiotensin II or oxygen-derived free radicals. However, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (50 microM; Ca++ chelating agent), 8-(diethyl-amino)octyl 3,4,5-trimethoxy benzoate (10 microM; intracellular Ca++ antagonist), or neomycin (5 mM; phospholipase-C inhibitor) abolished the vasoconstriction. Ouabain (0.5 mM) did not affect the vasodilation, but perfusion with excess (50 mM) or 0 K+ Krebs' solution abolished it, suggesting this PGI2 action involves changes in membrane K+ conductance via a mechanism independent of Na+/K+ adenosine triphosphatase. Vasodilation evoked by BRL 34915 (K+ channel activator) was similarly attenuated under these conditions, but not by ouabain. Furthermore, procaine (1 mM; nonspecific K+ channel inhibitor), but not apamin (0.5 microM) or tetraethylammonium (10 mM) blocked PGI2- and BRL 34915-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of vascular actions of prostacyclin in the rat isolated perfused mesenteric arteries. 210 93

The effect of suppression of prostaglandin synthesis on renal sodium handling and microsomal Na-K ATPase was studied in control and indomethacin treated intact rats maintained on a normal sodium diet (series A) and chronically salt loaded (series B). Indomethacin administration resulted in a decreased GFR and a significantly depressed urinary excretion and an increased fractional reabsorption of sodium in animals fed the normal sodium diet or chronically salt loaded. In rats maintained on a normal Na diet, the activity of the renal medullary Na-K ATPase after indomethacin was 206.3 +/- 6.4 ug Pi/mg protein, i.e. significantly higher as compared with the enzyme activity in the medullary renal fraction from control animals in which it averaged 148 +/- 7.79 ug Pi/mg protein (p less than 0.001). While after chronic salt load a similar increment in the activity of renal medullary Na-K ATPase was observed, no additional stimulation was elicited by subsequent indomethacin administration. The addition of exogenous PGE2, 0.1 mM to microsomal fractions obtained from kidneys of normal rats, was associated with a moderate suppression of the medullary Na-K-ATPase activity, from a basal level of 170 +/- 16 to 151.3 +/- 13 umol Pi/mg protein/hr (p less than 0.005). In isolated segments of medullary thick ascending limb of Henle's loop (MTAL) addition of PGE2 to the incubation medium resulted in a significant inhibition of Na-K ATPase from 37.2 +/- 2 to 21.25 +/- 1.17 x 10(-11) mol/mm/min (p less than 0.0001). These findings suggest that the increased renal Na reabsorption after inhibition of PG synthesis might be related, at least partly, to stimulation of medullary Na-K ATPase. In parallel, the reported natriuretic effect of prostaglandins might imply a direct inhibitory effect of these mediators on renal Na-K ATPase.
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PMID:Renal sodium handling and stimulation of medullary Na-K-ATPase during blockade of prostaglandin synthesis. 215 24

Erythrocyte sodium transport was evaluated by measurement of intracellular Na concentration (ICNa), 22Na efflux rate constant (NaERC) and 3H-ouabain binding (BMax) (reflecting the number of Na/K ATPase pump sites) in 9 children with Bartter's syndrome compared to controls (children and adults) and children with various forms of salt wasting disease. There were no differences between control children and adults. In untreated Bartter's syndrome ICNa was significantly increased with NaERC and BMax significantly decreased compared to findings in controls and patients with other salt wasting disease. On prostaglandin synthetase inhibitor (Indomethacin) therapy, ICNa decreased but remained higher than in controls, NaERC increased to normal values but BMax remained low. These data support the view that there is a widespread defect in membrane electrolyte transport in Bartter's syndrome but suggest that the benefit of indomethacin therapy is not manifest via an effect on Na/K ATPase.
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PMID:Erythrocyte sodium transport in Bartter's syndrome. 284 51

Timoprazole, a substituted benzimidazole, is an antisecretory agent that inhibits gastric acid secretion by interference with (H+-K+)-ATPase. In the studies reported herein, timoprazole given orally was found to be cytoprotective for the stomach when given 30 min prior to a challenge to boiling water, ethanol, or 0.6 N HCl. Timoprazole also prevented necrosis of the mucosa and acute ulcerations induced by alcohol in the rat fundus, as evaluated by histopathology. The ED50 for cytoprotection was between 1 and 3 mg/kg of timoprazole depending on the challenge, whereas the antisecretory ED50 was approximately 12 mg/kg. Timoprazole was an active antisecretory agent when given subcutaneously (ED50 10 mg/kg), but was not cytoprotective when given by this route. Indomethacin pretreatment (5 mg/kg orally) blocked the cytoprotective activity of oral timoprazole at doses of 1 or 3 mg/kg given 30 min later. However, at higher doses of timoprazole (5 mg/kg), indomethacin did not inhibit the cytoprotective activity. The ability of high doses of timoprazole to overcome the indomethacin blocks is different than the cytoprotective activity of mild irritants, which is always blocked by indomethacin. However, when tested in vitro, timoprazole exhibited only mild inhibitory activity on both prostaglandin cyclooxygenase and 15-hydroxyl-dehydrogenase and only at high doses, suggestive of nonspecific activity.
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PMID:Timoprazole is a unique cytoprotective agent in the rat. 609 83

Human peripheral blood leukocytes, activated by phorbol myristate acetate, disrupt canine sarcoplasmic reticulum calcium transport, in vitro, by an oxygen-derived free radical mechanism. Activated leukocytes significantly depress Ca++ uptake activity and Ca++ -stimulated, Mg++ -dependent ATPase activity. The depression is completely inhibited by sodium-azide (0.1 mM) or the combination of superoxide dismutase (10 micrograms/ml) and catalase (10 micrograms/ml). Exogenous hydrogen peroxide (0.441-4.41 mM) uncoupled Ca++ uptake activity from ATP hydrolysis, and this effect was inhibited by catalase. Mannitol alone did not inhibit the effects of activated leukocytes, but superoxide plus mannitol (20-100 mM) resulted in normal ATPase activity, while Ca++ uptake remained depressed. In the presence of indomethacin and ibuprofen, activated leukocytes depressed Ca++ uptake and had no effect on ATPase activity. 2-Amino-methyl-4-t-butyl-6-iodophenol (MK-447) further depressed Ca++ uptake and partially inhibited the effect on ATPase activity. Indomethacin plus catalase completely inhibited the effects of activated leukocytes on cardiac sarcoplasmic reticulum. We conclude, first, that activated leukocytes depress canine cardiac sarcoplasmic reticulum Ca++ transport by an oxygen-free radical mechanism with the generation of hydrogen peroxide and hydroxyl radical. In addition to the classical membrane NADPH oxidase system, significant oxygen radical generation can occur through the cyclooxygenase pathway of arachidonic acid metabolism, and seems to be responsible for the generation of the hydroxyl radical.
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PMID:Hydrogen peroxide and hydroxyl radical mediation of activated leukocyte depression of cardiac sarcoplasmic reticulum. Participation of the cyclooxygenase pathway. 613 70

1. Indomethacin inhibits calcium-stimulated adenosine triphosphatase (Ca2+-ATPase), calcium, magnesium-stimulated adenosine triphosphatase (Ca2+,Mg2+-ATPase) and magnesium-stimulated adenosine triphosphatase (Mg2+-ATPase) activities in rat brain synaptic vesicles in vitro. 2. The Ca2+-ATPase activity is most strongly affected by this drug all of the activities of ATPases tested. 3. The decrease of Ca2+-ATPase activity by addition of indomethacin is due to a decrease of Vmax. 4. The Ki values for this drug for ATP and Ca2+ in Ca2+-ATPase were 1.13 mM and 0.68 mM, respectively.
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PMID:Effect of indomethacin on Ca2+-stimulated adenosine triphosphatase in the synaptic vesicles of rat brain in vitro. 621 40


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