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 cytotoxic action of the S component of leukocidin from Staphylococcus aureus on rabbit polymorphonuclear leukocytes was supported by the following observations, (i) Leukocytes displayed a large chemotactic response to the S component (10(-10) M) as well as to the chemotactic factor N-formylmethionylleucylphenylalanine (10(-11) M). (ii) The S component stimulated high levels of phospholipase A2 activity in the cell membranes, with concomitant synthesis and release of prostaglandins. (iii) Uptake of 45Ca into leukocytes exposed to the S component was about double the rate of uptake into untreated cells. The increased 45Ca uptake into the cells was not inhibited by trifluoperazine and ruthenium red. (iv) Indomethacin and alloxazine, which had no effects on the binding of the S component to the cells, attenuated markedly the stimulation of phospholipase A2 activity, the syntheses of prostaglandins, and the increased uptake of 45Ca caused by the S component. The F component of leukocidin, bound to rabbit leukocytes with the aid of the S component, rapidly induced complete release of 86Rb from preloaded leukocytes. This release resulted from stimulation of ouabain-insensitive (Na+ + K+)-adenosine triphosphatase activity and inhibition of cyclic AMP-dependent protein kinase.
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PMID:Mode of action of staphylococcal leukocidin: effects of the S and F components on the activities of membrane-associated enzymes of rabbit polymorphonuclear leukocytes. 627 2

To assess Na-K-ATPase inhibiton and prostaglandin synthesis stimulation as the mechanism of the secretory (cathartic) action of phenolphthalein in the primate, we investigated water and electrolyte transport and Na-K-ATPase levels in monkey intestine. Both jejunum and colon were studied with in vivo perfusion and in vitro Ussing chamber techniques. Water, Na, and Cl absorption was inhibited or secretion was induced by phenolphthalein (10(-3) M) in the jejunum and colon when the drug was present in the mucosal bathing (perfusion) solution. Serosal addition of phenolphthalein (10(-4) or 10(-3) M) induced Na and anion absorption in the jejunum but not in the colon. Phenolphthalein inhibited Na-K-ATPase activity in the test tube, but assays of intestine previously perfused or bathed in the drug showed no inhibiton. Indomethacin, in doses sufficient to inhibit prostaglandin synthesis in the intestine, inhibited the secretion induced by phenolphthalein in the jejunum but not in the colon. These inconsistencies cast doubt on the role of Na-K-ATPase inhibition or the role of prostaglandin synthesis stimulation in the mechanism of action of phenolphthalein.
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PMID:Effect of phenolphthalein on monkey intestinal water and electrolyte transport. 628 79

1. The activity of the overall Na+-K+-ATPase reaction was inhibited by indomethacin in vitro. 2. The K+-NPPase activity was also inhibited by indomethacin. 3. The activity of Na+-dependent phosphorylation of Na+-K+-ATPase was activated by indomethacin. 4. Indomethacin required for 50% inhibition of K+-NPPase activity was 0.4 mM. 5. Inhibition mode of indomethacin for both the substrate and K+ in K+-NPPase reaction was competitive type. 6. The Ki values for indomethacin for the substrate and K+ in K+-NPPase reaction were 0.4 and 0.24 mM, respectively. 7. Inhibitory effect of indomethacin on K+-NPPase was reversible.
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PMID:Mode of inhibition of activity of Na+-K+-stimulated adenosine triphosphatase by indomethacin. 629 11

Effects of elevated potassium on bone resorption and on the inhibition by ouabain of parathyroid hormone (PTH)-stimulated resorption were studied in neonatal mouse calvaria, fetal mouse limb bones, and fetal rat limb bones. Ouabain inhibited PTH-stimulated resorption, and K at least partially reversed the inhibition by ouabain in all three systems. However, in contrast to calvaria, neither limb bone system was stimulated to resorb by increased K. Although the reversal of ouabain inhibition in all three systems was likely mediated by an effect on Na-K-ATPase, the resorptive effect of K alone must occur by a different mechanism because it was seen only in the calvaria. The production of prostaglandins may play a partial role in the mechanism of the stimulation of Ca release from calvaria by K. Potassium (35 mM) stimulated production of PGE2 by calvaria but not by limb bones. Indomethacin inhibited the increase in PGE2 in calvaria and partially blocked the stimulated bone resorption observed in response to K. The fetal rat limb bone cultures also differed from the mouse calvaria in being more readily inhibited by increased osmolarity. Thus, secondary effects may be responsible for the variant responses of different bone tissues to certain stimuli.
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PMID:Potassium effects on bone: comparison of two model systems. 660 61

Intraluminal perfusion of pig jejunum with Escherichia coli heat-stable enterotoxin reversed net absorption of water and electrolytes to net secretion. Addition of atropine (2 x 10(-5)M) to the perfusate reduced the secretory response to enterotoxin and enhanced sodium and chloride absorption in control segments. Indomethacin (1.4 x 10(-3)M), acetazolamide (2.2 x 10(-3)M), or ethacrynate sodium (3.1 x 10(-4)M) had no effect. Mucosal disaccharidase activity and Na-K-ATPase activity were not altered by enterotoxin. The results suggest that blockade of cholinergically mediated secretion in the small intestine attenuates the enterosorptive effects of heat-stable enterotoxin and may be useful therapeutically in the management of secretory diarrhea.
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PMID:Effects of indomethacin, acetazolamide, ethacrynate sodium, and atropine on intestinal secretion mediated by Escherichia coli heat-stable enterotoxin in pig jejunum. 675 23

To test the hypothesis that indomethacin, an inhibitor of cyclooxygenase, reduces free radical-induced brain cell membrane changes during cerebral hypoxia, we determined levels of brain cell membrane lipid peroxidation products and Na+,K(+)-ATPase activity as indicators of free radical production and membrane function, respectively, in 29 newborn piglets divided into 4 groups. Eight saline- and 4 indomethacin-treated normoxic animals served as controls; 8 saline-pretreated piglets and 9 piglets pretreated with indomethacin were exposed to hypoxic hypoxia for 60 min. Cerebral hypoxia was documented using 31P-NMR spectroscopy. In saline-pretreated hypoxic animals Na+,K(+)-ATPase activity decreased significantly and levels of membrane lipid peroxidation products increased significantly compared to normoxic controls. Indomethacin pretreatment prevented the hypoxia-induced increase in membrane lipid peroxidation products but had no effect on the decrease in Na+,K(+)-ATPase activity. Thus the apparent reduction in free radical production by indomethacin pretreatment did not prevent the hypoxia-induced change in Na+,K(+)-ATPase activity.
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PMID:Effect of cyclooxygenase inhibition on brain cell membrane lipid peroxidation during hypoxia in newborn piglets. 772 19

Indomethacin showed a dose-, time-, and pH-dependent, noncompetitive inhibitory effect on hog gastric H+/K(+)-ATPase. Four percent of total indomethacin in the buffer (0.20 mmol/liter) bound to the H+/K(+)-ATPase vesicles (15 micrograms/ml). It markedly quenched the intrinsic fluorescence of the enzyme, and decreased the membrane fluidity. Thus, the inhibitor effect of indomethacin may arise from both a direct effect on the hydrolytic and H+ transport functions of the enzyme and a disturbing effect on the lipid bilayer of the vesicle.
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PMID:Indomethacin inhibition of hog gastric H+/K(+)-ATPase arises from its effect on both the enzyme protein and the lipid bilayer. 782 39

Studies were designed to determine the extent of the involvement of endothelium-derived relaxing factor(s) other than nitric oxide (NO) in vascular relaxation in response to acetylcholine (ACh) in the rabbit renal artery. ACh (10(-9)-10(-6) M) induced concentration-dependent relaxation of isolated endothelium-intact arterial rings preconstricted with noradrenaline. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, partly inhibited the ACh-induced endothelium-dependent relaxation, whereas it almost completely abolished the production of cyclic-3', 5'-guanosine monophosphate (cGMP) in these rings in response to ACh. Methylene blue, an inhibitor of guanylate cyclase, had an essentially similar effect to L-NAME on the relaxation. Indomethacin, an inhibitor of cyclooxygenase, had no effect. High concentrations of potassium chloride (to inhibit endothelium-dependent hyperpolarization), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), a voltage-dependent or Ca(2+)-dependent K+ channel blocker, partly inhibited the relaxation while, in contrast, glibenclamide, an ATP-sensitive K+ channel blocker, had no effect. Ouabain, an inhibitor of Na+, K(+)-ATPase, also partly inhibited the ACh-induced relaxation, especially the higher concentration effect. Application of L-NAME together with ouabain, TEA, or a high concentration of potassium chloride completely abolished the relaxation. These results suggest that ACh-induced endothelium-dependent relaxation in the rabbit renal artery is mediated by NO, and by an other factor(s), which relaxes the vascular smooth muscle through opening K+ channels other than ATP-sensitive ones, and/or through the activation of a Na+, K(+)-pump.
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PMID:NG-nitro-L-arginine-resistant endothelium-dependent relaxation induced by acetylcholine in the rabbit renal artery. 804 Dec 28

As a noncompetitive inhibitor of pig gastric H+/K(+)-ATPase, indomethacin inhibited the H+ transportation function of the enzyme, leading to not only the obvious dissipation of H+/K(+)-ATPase-generated H+ gradients, but also the decreasing of the H+ gradient formation ability of the enzyme. 4% of indomethacin was able to penetrate into the lipid bilayer of H+/K(+)-ATPase vesicles at 0.15 mg/ml protein concentration, which showed an influence of indomethacin to the membrane. Indomethacin reduced the membrane fluidity of H+/K(+)-ATPase vesicles significantly. It also damaged the conformation of membrane protein extraordinarily, which was evidenced by decreasing the intrinsic fluorescence of H+/K(+)-ATPase. From the results, we suggest that the effect of indomethacin on H+/K(+)-ATPase is taken place by its inhibition on H+/K(+)-ATPase protein, as well as by its influence on the membrane lipid bilayer of H+/K(+)-ATPase vesicles.
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PMID:[Effect of indomethacin on H+ transportation of pig gastric H+/K(+)-ATPase]. 804 9

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


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