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)

Ethacrynic acid (10(-4) M) inhibits exocytosis, phagocytosis and superoxide release in rabbit polymorphonuclear leukocytes (PMN's). Dihydroethacrynic acid is a much weaker inhibitor of these PMN functions. Though ethacrynic acid inhibits ATPase activity in the PMN, this occur at much higher concentrations than required for inhibition of exocytosis and superoxide release, thus a causal relationship seems unlikely. The same applies to inhibition of ATP generation by ethacrynic acid: the concentration required to decrease ATP level in PMN's is much higher than required for the inhibitory effect on exocytosis. Inhibition of exocytosis by ethacrynic acid can be prevented by dithiothreitol. It is concluded that vulnerable sulfhydryl groups are involved in the inhibition by ethacrynic acid.
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PMID:Inhibition of some polymorphonuclear leukocyte functions by ethacrynic acid. 628 Jul 31

Ouabain (10(-3) M) caused a 95.8% reduction in the volume of saliva secreted during a 60-min period by the isolated, perfused submandibular gland of the rat exposed to acetylcholine (10(-6) M) and modified salivary cation (Na and K) concentrations but not salivary Cl concentrations. Furosemide (10(-3) M) caused a 74.9% reduction in saliva volume and significantly reduced salivary Cl concentrations but did not modify salivary Na or K. Ethacrynic acid (10(-4) M) resulted in a 58.6% reduction in saliva volume, increased salivary Na and Cl concentrations, and reduced salivary K+ concentrations at low rates of flow. The results suggest that an ouabain-sensitive Na+-K+-ATPase and a furosemide-sensitive NaCl cotransport system contribute to acetylcholine-induced fluid secretion in the rat submandibular gland. The Na+-K+-ATPase probably provides the energy or driving force for the NaCl cotransport system by maintaining a Na+ gradient in the salivary cells. The lesser effect of ethacrynic acid on saliva volumes may result from a quantitatively smaller action on the same NaCl cotransport affected by furosemide. An ouabain-sensitive pump present in salivary ducts regulates transductal transport of Na and K.
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PMID:Effect of transport inhibitors on secretion by perfused rat submandibular gland. 631 25

Ethacrynic acid inhibits energy-requiring transcellular NaCl reabsorption without affecting NaHCO3 reabsorption. Acetazolamide inhibits NaHCO3 and most of the remaining NaCl reabsorption in the proximal tubules (bicarbonate-dependent reabsorption) but raises distal transcellular NaCl reabsorption. After administration of both diuretics, the remaining bicarbonate-dependent and transcellular reabsorptions become constant until glomerular filtration rate (GFR) is almost halved. The inhibitory effect of expanding the extracellular volume (ECV) until plasma volume and GFR increased 30-40% was examined in anesthetized dogs. Examinations at comparable GFR obtained by altering arterial perfusion pressure showed that the inhibitory effect of ECV expansion was attenuated by administering acetazolamide. Ethacrynic acid amplified the inhibitory effect which for sodium and chloride reabsorption amounted to 6-7% of the filtered load at comparable GFR. An inhibitory effect of ECV expansion of bicarbonate reabsorption was disclosed only after raising plasma bicarbonate concentration. Thus, the small inhibitory effect of massive ECV expansion is confined to proximal tubular bicarbonate-dependent reabsorption and is of the same magnitude as previously demonstrated in experiments of similar design by raising plasma pH by only 0.07 unit. Since ouabain inhibits transcellular NaCl reabsorption, a natriuretic hormone is more likely to be an inhibitor of carbonic anhydrase than of Na,K-ATPase.
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PMID:Site and magnitude of the tubular inhibitory effect of expanding the extracellular volume in dogs. 651 81

The results obtained by biochemical measurement demonstrated for the first time that significant decrease of the plasma membrane Ca(2+)-ATPase activity occurred during capacitation and acrosome reaction of guinea pig sperm. Ethacrynic acid, one kind of Ca(2+)-ATPase antagonists, inhibited the plasma membrane Ca(2+)-ATPase activity, but calmodulin (50 micrograms/mL) and trifluoperazine (200-500 mumol/L) did not, suggesting that calmodulin is not involved in ATP-driven Ca2+ efflux from sperm. However, calmodulin is involved in the control of Ca2+ influx. TFP, one kind of calmodulin antagonists, accelerated the acrosome reaction and Ca2+ uptake into sperm cells significantly. Ca(2+)-ATPase antagonists, quercetin, sodium orthovandate, furosemide and ethacrynic acid promoted the acrosome reaction, but inhibited Ca2+ uptake, which cannot be explained by their inhibitory effects on the plasma membrane Ca(2+)-ATPase activity. It is speculated that this phenomenon might be caused by simultaneous inhibitions of the activities of Ca(2+)-ATPase present in the plasma membrane, the outer acrosome membrane and the outer mitochondrion membrane resulting in Ca2+ accumulation in the cytoplasm, which in turn blocks further Ca2+ entry through some negative feedback mechanism(s). The inhibitory effect of Ca(2+)-ATPase antagonist on glycolytic activity may also be the reason for Ca2+ accumulation in cytoplasm and inhibition of Ca2+ uptake.
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PMID:Relationship between plasma membrane Ca(2+)-ATPase activity and acrosome reaction in guinea pig sperm. 938 39

In the HeLa tumor cell line, we studied the characteristics of the dual effect of digitalis compounds on cell growth (proliferation and death). In addition, we explored whether both effects occur by means of the same mechanism. HeLa cell cultures were exposed to increasing concentrations (0.01 nM-10 microM) of ouabain, strophantidin, digoxin, and digoxigenin at 24-96 h intervals. Cell growth in treated cultures was compared with cell growth under nontreated conditions. Additionally, we studied changes in nuclear morphology, as well as in genomic DNA degradation, cytochrome c release, and caspase-9 and -3 presence and processing induced by toxic concentrations of digitalis. Digitalis compounds increased HeLa cell number when exposed to concentrations <10 nM during a 48 h period. Ethacrynic acid (a nonsteroid inhibitor for Na+/K+-ATPase) did not induce cell growth at these concentrations. Digitalis concentrations >10 nM induced cell death in a concentration- and exposure period-dependent fashion. Changes in nuclear morphology, DNA fragmentation, mitochondrial cytochrome c release, and proteolytic processing of caspases-9 and -3, suggest apoptotic cell death. The IC50 for the inducing effect of apoptosis by ouabain at 96 h was 18 nM and corresponds with the IC50 for the Na+/K+-ATPase inhibition in HeLa cells. In conclusion, the dual effect of digitalis compounds on HeLa cells growth is concentration and time-dependent. The apoptosis-inducing effect correlates with inhibition of Na+/K+-ATPase. Proliferation does not appear to be mediated through this pathway. The apoptosis-induction pathway is possibly cytochrome c-dependent.
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PMID:Proliferation and apoptosis of HeLa cells induced by in vitro stimulation with digitalis. 1650 6


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