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)

In humans and animals, the administration of Li or amiloride results in a defect in urinary acidification. Both agents are thought to cause this by a voltage-dependent mechanism in the distal nephron. This study was designed to determine the effects of chronic Li and amiloride administration on the two main transport enzymes in rat nephron collecting tubule, the Na-K-adenosine triphosphatase (ATPase) and the H(+)-ATPase. We also examined the effects of both agents on these enzymes in vitro. Amiloride administration resulted in a decrease in Na-K-ATPase and H(+)-ATPase activities in cortical collecting tubule and medullary collecting tubule. Therapeutic concentrations of amiloride in vitro inhibited Na-K-ATPase activity, but only in cortical collecting tubule. The effects of Li administration were different; it decreased Na-K-ATPase and H(+)-ATPase in both cortical collecting tubule and medullary collecting tubule. In cortical collecting tubule, the inhibitory effect on H(+)-ATPase activity was seen in vitro at a Li concentration similar to that found in urine. In contrast to the effect of Li on the H(+)-ATPase, in vitro Li stimulated Na-K-ATPase activity. These results suggest that the mechanism of action whereby these two agents result in distal renal tubular acidosis in humans and animals are different. In the collecting tubule, amiloride appears to act solely through a voltage-dependent mechanism by inhibiting cortical collecting tubule Na-K-ATPase. Li, by contrast, appears to have an additional effect in the cortical collecting tubule to inhibit the H(+)-ATPase. The biochemical differences seen with these drugs may explain the more severe acidemia universally found in animals after chronic Li administration.
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PMID:Effect of lithium and amiloride on collecting tubule transport enzymes. 131 62

Vanadate stimulated the release of rat hepatic lipase activity from liver slices into an incubation medium in a time- and dose-dependent manner. Insulin, however, failed to have this stimulatory action, and the release by heparin was recognized, but was not additive to that by vanadate. Amiloride, an inhibitor of tyrosine kinase in some receptors and of the Na+/H+ exchange system suppressed the vanadate-stimulated release. Biochanin A, a different type of tyrosine kinase inhibitor than amiloride, also suppressed the effect of vanadate. The stimulation by vanadate was clearly preserved in Na(+)-, K(+)-, or Ca(2+)-free medium, suggesting that neither the Na+/H+ exchange system, Na+, K(+)-adenosine triphosphatase, nor Ca(2+)-influx into cells is involved in the action of this substance. These results suggest that vanadate-stimulated release of the enzyme activity is associated with the activation of the tyrosine kinase activity.
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PMID:Vanadate-stimulated release of hepatic lipase activity from liver. 181 20

1. To determine whether alterations in membrane sodium transport in airway smooth muscle can alter its contractility, we studied the effect of ouabain (a Na+/K(+)-adenosine triphosphatase inhibitor) and amiloride on contractile responses in bovine trachea and human bronchial rings in a series of studies. 2. Ouabain (10(-6)-10(-4) mol/l) caused concentration-related contraction of bovine trachea with a maximum effect at 30 min; the mean increases in tension with 10(-6), 10(-5) and 10(-4) mol/l ouabain were 19, 27, and 32%, respectively, of the maximum response seen with 10(-3) mol/l histamine (n = 6). In human bronchial rings, ouabain (10(-5) mol/l) caused a mean contraction which was 40% of the maximum response to methacholine (n = 8). 3. Calcium-free fluid (plus ethylenediaminetetraacetic acid) and nifedipine (10(-5) mol/l) inhibited ouabain-induced contractions, suggesting that contraction was mediated in part by calcium entry via voltage-dependent calcium channels. Phentolamine (10(-5) mol/l) was without effect. 4. Ouabain (10(-5) mol/l) did not alter histamine responsiveness in bovine trachea or methacholine responsiveness in human bronchial rings. 5. Amiloride did not affect resting tone in bovine trachea but caused a concentration-dependent relaxation of bovine tracheal strips preconstricted with carbachol, 10(-3) mol/l amiloride relaxing strips completely over 15 minutes (n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of sodium-transport inhibitors on airway smooth muscle contractility in vitro. 217 51

Electrogenic Na absorption, independent of either nutrients or other ions, occurs in the rabbit ileum. However, unlike electrogenic Na absorption in the distal colon and other tight epithelia, this ileal transport system is not inhibited by amiloride. Because of this amiloride insensitivity, ileal electrogenic Na absorption has been poorly characterized. To more clearly delineate the underlying mechanisms of this pathway, we examined the effects of phenamil, an amiloride analogue, on ion fluxes and electrical parameters in rabbit ileum in vitro under short-circuit conditions. Phenamil has been shown to have a high affinity for Na channels, but minimal effect on Na-H exchange. Amiloride (10(-8) through 10(-4) M) had a minimal effect on short-circuit current. In contrast, phenamil induced a significant decrease in short-circuit current; the maximal effect was seen at 10(-4) M phenamil. There was an associated decrease in conductance at 10(-4) M phenamil. Ion flux studies were performed in normal, chloride-free and bicarbonate-free Ringer's solution; under each condition, 10(-4) M phenamil inhibited mucosal-to-serosal Na flux, net Na flux, and short-circuit current without significantly altering other fluxes. Phenamil did not inhibit the electrical response to either 10 mM glucose or 1 mM theophylline, indicating that the drug did not block either nutrient-coupled electrogenic Na absorption or electrogenic Cl secretion, and did not inhibit sodium-potassium-stimulated adenosine triphosphatase. These results demonstrate that electrogenic Na absorption in rabbit ileum may be blocked by the amiloride analogue phenamil, suggesting that, in this epithelium, Na absorption may occur via Na channels in which the amiloride-binding site has been significantly altered.
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PMID:Phenamil inhibits electrogenic sodium absorption in rabbit ileum. 253 78

The relaxant action of amiloride was investigated in the smooth muscles of guinea pig taenia ceci and chicken gizzard. Amiloride inhibited the contractions induced by high K+ (45.4 mM) and carbachol (10 microM) in the taenia with the concentrations needed to induce 50% inhibition (IC50) of approximately 41 microM. A prolonged incubation period (greater than 1 hr) was necessary to obtain the full inhibition of these contractions. The taenia gradually accumulated amiloride and the tissue/medium ratio exceeded 2.0 after a 120-min incubation period. Amiloride had no effect on the high K+-stimulated 45Ca++ uptake or the ATP content of the taenia. Amiloride inhibited the Ca++-induced contraction of the saponin-treated taenia with an IC50 of 186 microM. Amiloride (10-1000 microM) also inhibited superprecipitation and Mg++-adenosine triphosphatase activity of the gizzard native actomyosin as well as the phosphorylation of myosin light chain. The inhibition of the phosphorylation was antagonized competitively by ATP. Amiloride (1 mM) had no effect on the dephosphorylation of myosin light chain upon removal of Ca++ from reaction medium. Amiloride, at concentrations up to 1 mM, had not effect on calmodulin activity as monitored by the Ca++-calmodulin-activated erythrocyte membrane (Ca++ + Mg++)-adenosine triphosphatase and phosphodiesterase activities. In contrast to this, trifluoperazine inhibited the calmodulin activity at the concentration needed to inhibit the Ca++-induced contraction of the permeabilized taenia and the superprecipitation and the phosphorylation of myosin light chain of gizzard. We conclude that amiloride, unlike trifluoperazine, may inhibit directly the myosin light chain kinase activity to induce muscle relaxation.
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PMID:Inhibition by amiloride of contractile elements in smooth muscle of guinea pig taenia cecum and chicken gizzard. 282 5

A 6.5-kilobase fragment of genomic DNA from mutant mouse cells under ouabain selection pressure conferred ouabain resistance when transfected into ouabain-sensitive CV1 green monkey fibroblasts. Ouabain resistance was induced in the presence of 10 microM ouabain. Amiloride (500 microM) completely blocked ouabain-insensitive 86Rb+ uptake into these cells. Plasma membranes from these cells demonstrated little sodium-dependent adenosine triphosphatase (ATPase) activity but had potassium-dependent and ouabain-resistant p-nitrophenylphosphatase activity. Like Na+,K+-ATPase this activity was vanadate- and sodium-inhibitable. Also, like the Na+,K+-ATPase, sodium inhibition of the p-nitrophenylphosphatase was reversed by 10 microM adenosine 5'-triphosphate.
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PMID:Membrane biochemistry of the ouabain-resistant potassium transport system. 282 73

In the present study we investigated the effect of amiloride, a rather specific inhibitor of the membrane Na+-Ca++ exchange system, on the release of endogenous dopamine (DA) and "previously taken-up" [3H]DA from tuberoinfundibular dopaminergic neurons. Amiloride (300 microM) stimulated either endogenous DA or [3H]DA release. Amiloride-induced stimulation of [3H]DA release was prevented in a Ca++-free plus ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid medium. Amiloride, at the same concentration, reinforced both high K+- and electrically-induced stimulation of [3H]DA release. These results are explained on the basis of the ability of amiloride in blocking the Na+-Ca++ exchange system, therefore causing an elevation of intracellular Ca++ levels in resting conditions, and a further accumulation of Ca++ ions after high K+- or electrically elicited opening of voltage-operated channels specific for Ca++ ions. The enhanced intracellular Ca++ availability may trigger the stimulation of neurotransmitter release. In addition, amiloride was able to block in a dose-dependent manner (70-300 microM) the ouabain-induced [3H]DA release, suggesting that, when intracellular concentrations of Na+ are increased by the blockade of Na+,K+-adenosine triphosphatase the Na+-Ca+;+ exchange carrier reverses its resting mode of operation, mediating the influx of extracellular Ca++ ions. Amiloride, by blocking the Na+-Ca++ exchange mechanism, prevents the ouabain-elicited entrance of extracellular Ca++ ions, therefore inhibiting [3H]DA release stimulated by the cardioactive glycoside. Collectively, the results of the present study seem to be compatible with the idea that the Na+-Ca++ exchange mechanism is involved in the regulation of [3H]DA release from tuberoinfundibular dopaminergic neurons, through the regulation of Ca++ movements across the plasma membrane.
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PMID:Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. II. Effect of the inhibition of the Na+-Ca++ exchange by amiloride. 284 53

The accumulation of Ldopa, dopamine (DA) and 3,4-dihydroxyphenylacetic (DOPAC) in kidney slices loaded with Ldopa (10-100 microM) was found to be dependent on the concentration of sodium in the medium (0-160 mM). The constant rate of accumulation did not depend on the concentration of Ldopa used and was about 0.0025, 0.0035 and 0.0065 for Ldopa, DA and DOPAC, respectively. In experiments performed in the presence of 120 and 160 mM sodium, but not with 20 mM sodium in the medium, ouabain (500 and 1000 microM) and amphotericin B (10 and 50 micrograms/ml) significantly reduced the accumulation of both DA and DOPAC (6-21 and 29-56% reduction, respectively). Amiloride (5-100 microM) produced an increase in the accumulation of DA and drastically reduced the formation of DOPAC. This effect was found to be due to inhibition of monoamine oxidase. During monoamine oxidase inhibition ethylisopropylamiloride (1, 5 and 10 microM), but not amiloride (10 and 50 microM), increased the accumulation of newly formed DA in kidney slices and reduced the outflow of the amine into the incubation medium. In conclusion, the results presented here show that the formation of DA in kidney slices loaded with Ldopa is dependent on the concentration of sodium in the medium and sensitive to the inhibition of the enzyme Na(+)-K+ adenosine triphosphatase and activation of mechanisms which bypass the tubular transport of sodium.
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PMID:Studies on the role of sodium on the synthesis of dopamine in the rat kidney. 838 Aug 67

We investigated the nature of the light-induced, sodium-dependent acidification of the medium and the uptake of sodium by Synechococcus. The rate of acidification (net H(+) efflux) was strongly and specifically stimulated by sodium. The rates of acidification and sodium uptake were strongly affected by the pH of the medium; the optimal pH for both processes being in the alkaline pH range. Net proton efflux was severely inhibited by inhibitors of adenosine triphosphatase activity, energy transfer, and photosynthetic electron transport, but was not affected by the presence of inorganic carbon (C(i)). Light and C(i) stimulated the uptake of sodium, but the stimulation by C(i) was observed only when C(i) was present at the time sodium was provided. Amiloride, a potent inhibitor of Na(+)/H(+) antiport and Na(+) channels, stimulated the rate of acidification but inhibited the rate of sodium uptake. It is suggested that acidification might stem from the activity of a light dependent proton excreting adenosine triphosphatase, while sodium transport seems to be mediated by both Na(+)/H(+) antiport and Na(+) uniport.
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PMID:Nature of the light-induced h efflux and na uptake in cyanobacteria. 1666 87