Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ouabain, a specific sodium-potassium dependent adenosine triphosphatase (Na+-K+-ATPase) inhibitor, on antigen-induced histamine release was studied using guinea pig lung fragments sensitized in vitro with rabbit antibodies against bovine serum albumin. Histamine was assayed spectrofluorometrically. When sensitized tissue had been preincubated with ouabain (less than or equal to 1.0 x 10(-4) M) for 10 min prior to antigenic challenge, release of histamine was significantly inhibited (maximum 54%, p less than 0.001, N=9, paired t test). The most significant inhibition was obtained near the optimal concentration of antigen. The inhibition was dependent on the length of preincubation (less than or equal to 20 min), and was partially reversible upon washing the tissue removing the ouabain. Ouabain did not seem to prolong the duration of the histamine release process. Increase in potassium ion (less than or equal to 1.1 x 10(-2)M) inhibited the histamine release and had additive effects to ouabain action. Dibutyryl cyclic AMP (less than or equal to 5 x 10(-3) M), which could enhance the release, strongly antagonized the inhibition. Glucose removal from the medium did not abolish the ouabain effect. The results seem to indicate that immunologic release of histamine is under the influence of the membrane Na+-K+-ATPase activity.
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PMID:Inhibition of antigen-induced histamine release by ouabain. 5 30

Gram-negative endotoxin (Escherichia coli, 4 mg/kg) was found to produce a sustained fall in systemic arterial pressure, left ventricular pressure, and cardiac output that could be blocked by the histamine antagonist diphenhydramine. Histamine infusion was found to produce a parallel depression of systemic arterial pressure. Further, endotoxemia was found to produce a significant depression of myocardial contractility (dP/dt max) that could also be blocked by diphenhydramine. Cardiac myofibrillar adenosine triphosphatase (ATPase) activity from endotoxin-shocked hearts was found to be depressed, ATPase activity from subendocardial myofibrils being more depressed than that from subepicardial myofibrils. Myofibrillar ATPase activity was significantly protected by pretreating the animals with diphenhydramine. It is concluded that the initial hemodynamic phase of endotoxin shock is histamine-mediated and that this hemodynamic depression can be blocked with diphenhydramine. Further, it appears that endotoxin is capable of depressing myocardial contractility by depressing contractile protein function (myofibrillar ATPase activity)--the subendocardial surface more so than the subepicardial surface--and this depression of myocardial contractility can be blocked with diphenhydramine.
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PMID:Diphenhydramine protection of the failing myocardium during gram-negative endotoxemia. 15 4

1. We have recently shown that ouabain, an inhibitor of Na+/K(+)-adenosine triphosphatase, causes contraction of bovine and human airways in vitro, and that amiloride causes relaxation and inhibits receptor-operated contraction in bovine trachealis. 2. To determine whether such drugs alter bronchial reactivity in vivo, we have studied the effect of oral digoxin (an inhibitor of Na+/K(+)-adenosine triphosphatase) and oral and inhaled amiloride on bronchial reactivity to histamine in three double-blind, placebo-controlled studies. 3. Histamine reactivity was measured as the provocative dose causing a 20% reduction in the forced expiratory volume in 1 s (PD20FEV1) or, when normal subjects were included, the provocative dose causing a 35% reduction in the specific airways conductance (PD35sGaw); the results are given as geometric mean values. 4. In study 1, 13 atopic asthmatic subjects were given 20 mg of oral amiloride or placebo on separate days. Two hours after the drug, the geometric mean PD20FEV1 for histamine was 0.43 mumol after amiloride and 0.54 mumol after placebo (95% confidence intervals for the difference: 0.9 to -0.2 doubling doses of histamine; P = 0.2). 5. In study 2, six normal and 24 atopic asthmatic men inhaled 10 ml of 10(-2) mol/l amiloride or diluent control in a crossover study. The mean values of PD35sGaw for histamine immediately after inhalation of amiloride and placebo were 3.0 mumol and 4.3 mumol, respectively, in the normal subjects (95% confidence intervals for the difference: -0.53 to 1.52 doubling doses, P = 0.2), and 0.33 mumol and 0.29 mumol in the asthmatic subjects (95% confidence intervals for the difference: -0.95 to 0.57 doubling doses; P = 0.6).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of sodium-transport inhibitors on bronchial reactivity in vivo. 217 52

The mechanism of stimulatory action of histamine on gastric alkaline secretion was investigated in anesthetized rats. Intravenous infusion of histamine (2-8 mg/kg/hr) dose-dependently stimulated acid secretion and in the presence of omeprazole (60 mg/kg), an H+/K+-adenosine triphosphatase inhibitor, produced an increase of gastric but not duodenal alkaline secretion; the degree of gastric alkalinization was also dependent on the dose of histamine, reaching the maximal values of approximately 1.0 microEq/10 min. Cimetidine (100 mg/kg s.c.) significantly inhibited both acid and alkaline secretory responses caused by histamine, whereas indomethacin (5 mg/kg s.c.) significantly prevented the increased alkaline secretion caused by histamine as well as mucosal acidification (100 mM HCl for 10 min). Tripelennamine (10 mg/kg s.c.) had no effect on either acid or alkaline secretion. Histamine (8 mg/kg/hr) reduced the arterial blood pressure (25.3%) and increased the mucosal vascular permeability in the stomach as determined by Evans blue (160%), but these vascular responses were significantly prevented only by tripelennamine, excluding the possible contribution of the vascular effects to the increased gastric alkaline secretion. These results suggest that histamine may stimulate gastric alkaline secretion as well as acid secretion, and the mechanism of histamine-induced alkaline secretion may involve both endogenous prostaglandins and stimulation of H2-receptors.
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PMID:Stimulation of gastric alkaline secretion by histamine in rats: possible involvement of histamine H2-receptors and endogenous prostaglandins. 291 81

Histamine-stimulated gastric acid secretion involves a transient elevation of intracellular Ca(2+) and the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) cascade through phosphorylation, the actions of which ultimately result in the fusion of vesicles containing H,K-ATPase (adenosine triphosphatase) to the apical plasma membrane of parietal cells. To dissect the signaling events underlying gastric acid secretion, we have developed a permeabilized gastric gland model using streptolysin O (SLO). The advantage of this model is its ability to retain cytosolic components that are required for the secretory machinery while granting accessibility for the introduction of macromolecules into the cytoplasm. Our studies showed that acid secretion in SLO-permeabilized glands is a cAMP-dependent process and involves the recruitment of H,K-ATPase-rich tubulovesicles into the apical plasma membrane as judged by biochemical assays. These studies established a functional permeabilized gland model in which the resting-to-secreting transition can be triggered by second messengers, while the manipulation of the cytoplasmic environment can be achieved with ease.
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PMID:Molecular dissection of HCl secretion in gastric parietal cells using streptolysin O permeabilization. 1836 48