Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of two antiarrhytmic drugs, moracizine (MOR, CAS 31883-05-3) and ethacizine (ETHA, CAS 33414-33-4) on receptors of potential-operated CA-channels has been investigated. ETHA binding to verapamil receptors was more effective than that of MOR (IC50 = 0.53 +/- 0.08 mumol/l, respectively). The Hill coefficient for ETHA binding was similar to that of verapamil (0.64 +/- 0.09 and 0.60 +/- 0.10, respectively). Interaction of ETHA and MOR with dihydropyridine receptors in concentrations up to 10 mumol/l was similar that of verapamil, however, MOR was less potent. MOR and ETHA did not interact with calmodulin and troponin C at concentrations up to 100 mumol/l. The influence of MOR and ETHA on enzymes dependent on Ca-binding proteins (phosphodiesterase and actomyosin ATPase) was not observed up to 100 mumol/l. Comparison of clinical and electrophysiological data with these results allows the conclusion that ETHA exerts Ca-blocking effects by the interaction with verapamil receptors on potential-operated Ca-channels.
 ...
PMID:Effect of moracizine and ethacizine on receptors of potential-operated calcium channels and calcium-binding proteins. 132 68

20R 14 beta-amino 3 beta-rhamnosyl 5 beta-pregnan 20 beta-ol (LND 623, CAS 90520-42-6) was investigated and compared to digoxin in anesthetized dogs. The hemodynamic profiles showed: a) a pure positive inotropic action of LND-623; b) its potency was four-fold higher than that of digoxin and more marked in heart failure; c) its duration of action was maintained for at least 6 h. The onset and reversal of the inotropic effects of a single dose (3.3 nmol.kg-1.min-1) were faster with LND-623 than those of digoxin. This reversal is consistent with the faster dissociation profile observed at the level of the high affinity cardiac Na+,K(+)-ATPase receptor form. The advantage of LND-623 over digoxin resides in its larger therapeutic index (ratio of arrhythmogenic to inotropic responses) in anesthetized dogs with propranolol-induced heart failure. This index was 6 for LND-623 and 2 for digoxin.
 ...
PMID:Efficacy and safety of the novel Na+,K(+)-ATPase inhibitor 20R 14 beta-amino 3 beta-rhamnosyl 5 beta-pregnan 20 beta-ol in a dog model of heart failure. 133 48

Na(+)-K(+)-dependent ouabain-sensitive ATPase and Mg(2+)-ATPase activities have been assayed in brain and kidney of healthy and Schistosoma mansoni-infected mice before and after praziquantel (EMBAY 8440, CAS 5526874-1) treatment. Schistosoma mansoni infection caused a moderate decrease of brain Na(+)-K(+)-ATPase activity with a marked inhibition of its Mg-stimulated ATPase. Meanwhile, a marked inhibition in both renal ATPase activities was observed in infected mice. Treatment of the infected mice with praziquantel (2 x 500 mg/kg b.wt.) reversed the inhibitory effect of infection on brain and kidney ATPase, so that the activity of both renal ATPase and that of brain Mg-ATPase were nearly corrected while the activity of brain Na(+)-K(+)-ATPase was increased to an extent greater than normal values. However, treatment of normal mice with praziquantel did not affect any of the measured parameters. Possible explanations of these findings are given.
 ...
PMID:Effect of praziquantel treatment on brain and kidney ATPase activities in healthy and schistosoma mansoni-infected mice. 133 99

The effect of digitoxin (CAS 71-63-6) and ouabain (g-strophantin, CAS 630-60-4) on respiration, morphology and beating activity of cardiomyocytes in culture derived from embryonic chick hearts has been investigated. The drugs were applied in a perfusion system using a protein- and substrate-free perfusion medium (BSS) at two concentration of K+ (5.4 and 4 mmol/l). In either K+ concentration oxygen consumption was 0.13 +/- 0.05 nmol O2 h-1 per 1000 cells. During 3 h of perfusion with BSS oxygen consumption declines only slightly to 79 +/- 15% of the initial value. No relation was found between beating frequency and oxygen consumption. Increase in respiration ranged from 5 to 45% and lasted between 5 and 120 min. At concentrations being inhibitory to the Na+/K(+)-ATPase (greater than or equal to 1 mumol/l) ouabain stimulated respiration by about 20% at 4 mmol/l K+ and 10% at 5.4 mmol/l K+ while digitoxin was effective at 5.4 mmol/l only (a transient increase of 20%). At 0.1 nmol/l, (a concentration below the KD of the high affinity binding site of the Na+/K(+)-ATPase) ouabain caused a long lasting activation of respiration by about 30%, digitoxin induced a transient rise of up to 20% at 5.4 mmol/l K+. At 4 mmol/l K+ digitoxin did not affect respiration while ouabain caused a transient increase. The lowest concentration of ouabain inducing a reproducible activation of oxygen consumption was 0.1 pmol/l. At this concentration digitoxin was no longer effective. At 1 fmol/l respiration was stimulated only occasionally.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of ouabain and digitoxin on the respiration of chick embryo cardiomyocytes in culture. 185 11

Omeprazole (CAS 73590-58-6), an H+, K+ ATPase inhibitor, is a potent suppressor of gastric acid secretion and a very active substance in the treatment of duodenal and gastric ulcers. The kinetic profile of omeprazole is well defined for healthy volunteers and for some high-risk population, but not so far for patients with liver disease. As the substance is mainly metabolized in the liver, changes in liver circulation and/or function might lead to changes in the pharmacokinetics of omeprazole. Aim of the study was to evaluate the kinetic profile in patients with liver disease and compare the results obtained in healthy volunteers, 16 subjects were included in the study: 8 patients with liver cirrhosis and 8 healthy volunteers. A single oral dose of omeprazole 20 mg was administered: plasma samples were collected for 24 h since omeprazole administration. The principal pharmacokinetic parameters were estimated for the two studied populations.
 ...
PMID:Pharmacokinetics of omeprazole in cirrhotic patients. 185 16

Liver tumor nodules were induced by the administration of diethylnitrosamine [(DENA) CAS: 55-18-5; N-nitrosodiethylamine] to the fish, Oryzias latipes. A histochemical study showed decreased ATPase and glucose 6-phosphatase (Glc-6-Pase) activities in most of the tumor nodules. Increased ATPase staining and, occasionally, Glc-6-Pase staining were also observed. In some nodules, the distribution of bile canaliculi was disordered, indicating positive ATPase activity. Basophilic and eosinophilic nodules could be discriminated by histologic examination. The observations on serial histochemical and histologic sections revealed extreme heterogeneity in the phenotypes of the nodules. Measurement of the enzyme-altered areas indicated that the development of nodules was more prominent in male than in female fish. Experiments with sex-reversed fish, XX males and XY females, suggested that the sex difference in the susceptibility to DENA does not result from the difference in sex chromosomes but from the difference in sexual phenotypes.
 ...
PMID:Histochemistry of liver tumors induced by diethylnitrosamine and differential sex susceptibility to carcinogenesis in Oryzias latipes. 299 31

The livers of male inbred F344 rats fed Wy-14,643 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (CAS: 50892-23-4) in the diet at a concentration of 0.1% (wt/wt) were examined sequentially at 5, 10, 17, 21, 26, 30, 35, 40, 52, 60, and 70 weeks. At 5 weeks the livers were markedly enlarged and histologically showed markedly enlarged hepatocytes with prominent nucleoli. At 21 weeks altered acidophilic areas were seen in 2 of 3 animals that were killed. Between 26 and 52 weeks neoplastic nodules were noted of 1-8 mm containing cells with morphologic features similar to those observed in altered areas. Hepatocellular carcinomas (HCC) were observed in 1 animal killed at 30 weeks and in all the animals sacrificed at 60 weeks and later. [3H]thymidine nuclear labeling studies showed marked proliferative activity of cells in altered areas, neoplastic nodules, and HCC. Altered areas, neoplastic nodules, and HCC were consistently negative for gamma-glutamyltransferase and showed decreased ATPase activity. Glucose-6-phosphatase (Glc-6-Pase) activity was decreased in altered areas and neoplastic nodules. However, some of the HCC showed a strong positive reaction for Glc-6-Pase.
 ...
PMID:Sequential histologic study of rat liver during peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]-acetic acid (Wy-14,643)-induced carcinogenesis. 659 91

The potential promoting and/or complete carcinogenic activity of a methyl group-deficient (MD) diet lacking methionine, choline, vitamin B12, and folate on liver tumor induction in weanling male F344/NCr rats was examined. Each of 50 rats per group received one injection 20 mg diethylnitrosamine [(DENA) CAS: 55-18-5; N-nitrosodiethylamine]/kg body weight at 4 weeks of age, and then each was maintained on a methyl group-adequate (MA) diet for 52 weeks (groups 2 and 5) or on an MD diet for 15 weeks followed by the MA diet for 37 weeks (group 4). Controls received injections of saline and were maintained on the same two respective diet regimens (groups 1 and 3, respectively). Histologic results from sacrifices at 6, 10, 15, 22, 39, and 52 weeks revealed early development of foci of eosinophilic gamma-glutamyltransferase (GGT)-positive hepatocytes by week 6 in DENA-MD diet-treated rats, with subsequent development of a diffuse hyperplasia of hepatocytes, oval cell proliferation, cholangiofibrosis, nodular cirrhosis, and neoplastic nodule (NN) formation and, at 52 weeks, hepatocellular carcinomas (HCC) in 13 of 15 rats. Similar but significantly fewer lesions were observed at slightly later sacrifice times in the livers of saline-MD diet-treated rats, with development of NN in 5 of 12 rats and an HCC in 1 of 12 rats at 52 weeks. DENA-treated rats on MA diets developed relatively few GGT-positive foci, and none developed any neoplastic lesions. Except for basophilic foci, areas and foci of cellular alteration containing glycogen-rich hepatocytes frequently exhibited diminished uptake of injected iron and decreased glucose-6-phosphatase and ATPase contents focally or throughout. This study indicates that a relatively brief exposure of both untreated and DENA-treated weanling rats to a severely MD diet produces classical preneoplastic and neoplastic lesions in their livers.
 ...
PMID:Profound postinitiation enhancement by short-term severe methionine, choline, vitamin B12, and folate deficiency of hepatocarcinogenesis in F344 rats given a single low-dose diethylnitrosamine injection. 659 43

The effects of the cardiotonic agent pimobendan (CAS 118428-36-7, UD-CG 115 BS) and its main metabolite UD-CG 212 on dog cardiac myofibrillar calcium responsiveness and ATPase activity were studied at nominal free inorganic phosphate (Pi) and at 5 mmol/l Pi. A rightward shift of the pCa-tension relationship with a marked depression of maximal tension was observed in the presence of 5 mmol/l Pi. Pimobendan increased myofibrillar calcium responsiveness at concentrations > or = 10(-5) mol/l. These effects of pimobendan were significantly greater at 5 mmol/l Pi than at nominally free Pi. UD-CG 212 had no influence on myofibrillar calcium responsiveness at nominally free Pi, however, significant effects were observed at 10(-9) mol/l UD-CG 212 in the presence of 5 mmol/l Pi. UD-CG 212 (10(-8) mol/l) did not influence myofibrillar ATPase activity at pCa's 6.23, 5.99, and 4.36 with or without 5 mmol/l Pi, whereas pimobendan (10(-4) mol/l) had an effect only at pCa = 5.99 (without Pi) and pCa = 4.36 (+ 5 mmol/l Pi). The data suggest that the increase in myofibrillar calcium responsiveness at submaximal calcium concentrations by pimobendan and UD-CG 212 in the presence of 5 mmol/l Pi is brought about by a change in cross-bridge kinetics or by enhancement of thin filament activation by adjacent strong cross-bridges. At maximal calcium activation, pimobendan may additionally increase the population of strong cross-bridges.
 ...
PMID:Effects of pimobendan and its metabolite on myofibrillar calcium responsiveness and ATPase activity in the presence of inorganic phosphate. 771 Apr 34

The effect of leminoprazole ((+-)-2-[[2-(isobutyl-methylamino)benzyl]sulfinyl]-1H-benzimidazol e, NC-1300-O-3, CAS 104340-86-5), a new compound being developed as an inhibitor of the gastric mucosal proton pump (H+,K(+)-ATPase), on gastric mucus secretion was studied by a biochemical method measuring the gastric mucin content in rats. Oral administration of leminoprazole (30 mg/kg) strongly inhibited the hemorrhagic lesions induced by 60% ethanol containing 0.15 mol/l HCl (acid-ethanol) administered 1 h later. Leminoprazole significantly inhibited the acid-ethanol-induced reduction of the mucin content in the surface mucosa including the mucus gel layer, but no significant effect could be obtained on the reduction of mucin present in the deep layer of the corpus and antral mucosa. Leminoprazole given to rats not treated with acid ethanol accelerated the secretion of deep mucosal mucus and increased significantly the content of soluble mucus which was recovered from the gastric luminal contents to about 200% of control, but failed to produce any significant change in the mucus content present in the surface mucosal and the mucus gel layers. The effect of leminoprazole on gastric mucus secretion might contribute to healing the peptic ulcer diseases and may be involved in the cytoprotective mechanism of this drug.
 ...
PMID:Effect on gastric mucus of the proton pump inhibitor leminoprazole and its cytoprotective action against ethanol-induced gastric injury in rats. 794 16


1 2 Next >>