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)

Monensin concentrations between 0.5 and 30 microM produced dose-dependent positive inotropy when administered to normal, electrically driven rabbit left atria. These doses did not produce contracture. When monensin was combined with very low concentrations of ouabain (10 or 50 nM), irreversible contracture, irregular responses to electrical stimulation, or both, occurred in a significant number of atria treated with both drugs. This was apparently due to intracellular Na+ overload produced by both drugs, with secondary elevations of intracellular Ca++ concentrations. Monensin (17 nM, 1.7 or 170 microM) did not inhibit canine myocardial Na+mK+-adenosine triphosphatase activity. When administered to mitochondria isolated from normal rabbit hearts, monensin concentrations greater than 10 nM significantly depressed ADP-stimulated (State 3) respiratory rates and calculated respiratory control ratios. Maximum inhibition of the respiratory control ratio (85% decrease) occurred with monensin concentrations of 1 microM or more. These concentrations also significantly decreased calculated ADP:0 ratios. The data show that monensin concentrations required to increase contractility of isolated myocardium can produce marked inhibitory effects on isolated mitochondria, but apparently do not do so when the drug is administered to intact, normal cardiac tissue.
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PMID:Subcellular actions and potential adverse cardiac effects of the cardiotonic ionophore monensin. 624 11

The rate of development of the positive inotropic action of ouabain is enhanced when the heart is stimulated at higher frequencies. A hypothesis that this enhancement is due to a stimulation of the glycoside binding to sarcolemmal Na+,K+-adenosine triphosphatase (ATPase) caused by an increase in intracellular Na+ available to the sodium pump was tested in isolated left atrial muscle preparations of guinea-pig heart, incubated at 30 degrees C and electrically stimulated at 0.5, 1 or 2 Hz. The rate of development of the positive inotropic action of ouabain was dependent on the frequency of stimulation. Each preparation was homogenized at a predetermined time and the fractional occupancy of Na+,K+-ATPase by ouabain was estimated from the decrease in the initial velocity of ATP-dependent [3H]ouabain binding reaction. A parallel relationship was observed between effects of stimulation frequency of the positive inotropic action and those on the occupancy of Na+,K+-ATPase by ouabain. In quiescent preparations, a sodium ionophore, monensin, enhanced the development of contracture caused by a toxic concentration of ouabain and also the glycoside binding to Na+,K+-ATPase. Similar effects on the ouabain-induced contracture and on the glycoside binding were observed with either grayanotoxin I or batrachotoxin, agents known to increase sodium influx, when muscle preparations were exposed to these agents under 1.5 Hz stimulation and were subsequently tested for the actions of ouabain in quiescence. When the exposure to ouabain and either grayanotoxin I or batrachotoxin was restricted to quiescent period, the development of ouabain-induced contracture and glycoside binding to Na+,K+-ATPase were not significantly altered. Monensin, grayanotoxin I or batrachotoxin failed to significantly affect [3H]ouabain binding to muscle homogenates when added to the medium for the labeled glycoside binding assay. These results indicate that intracellular sodium ions promote the ouabain binding to Na+,K+-ATPase and thereby enhance the development of glycoside actions in the isolated atrial muscle of guinea-pig heart. The "beat-dependent" onset of the glycoside action is at least partially explained from the effect of membrane depolarization to increase Na+ available to the sodium pump and to enhance the glycoside binding.
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PMID:Enhancement of cardiac actions of ouabain and its binding to Na+, K+-adenosine triphosphatase by increased sodium influx in isolated guinea-pig heart. 629 Jun 40

A possibility that intracellular Na+ ions available to Na+,K+-adenosine triphosphatase influence the action of digoxigenin to cause sodium-pump inhibition and a positive inotropic effect was examined with isolated left atria of guinea-pig hearts. The positive inotropic action of digoxigenin developed more rapidly when atria were stimulated at 3 Hz than at 1.5 Hz. The rate of development of the positive inotropic action was dependent on the frequency of membrane depolarizations rather than on contractions. Monensin, a known Na+ ionophore, enhanced the rate of development of the positive inotropic action of digoxigenin. Sodium pump activity, as estimated from ouabain-sensitive 86Rb uptake, was inhibited by digoxigenin in a concentration-dependent manner in quiescent atria. The inhibition was enhanced by electrical stimulation which shifted the concentration-inhibition curves to the left. The sensitivity of the sodium pump for digoxigenin was also affected by membrane depolarizations, suggesting a role for intracellular Na+. These data indicate that similar to the cardiac glycosides, the interaction of the aglycone with Na+,K+-adenosine triphosphatase is essential for the development of the positive inotropic action of this agent.
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PMID:Positive inotropic action of digoxigenin and sodium pump inhibition: effects of enhanced sodium influx. 735 59

Monensin, a sodium specific ionophore was evaluated for its in vitro effects on rat testis by studying changes at biochemical parameters as well as at the DNA level. It was observed that monensin produced marked alterations in the activities of various enzymes associated with the testicular functions. The significant inhibition of different enzymes of oxidative defense system points toward the generation of reactive oxygen species (ROS) by monensin treatment. The significant depletion of reduced glutathione and elevation in the level of lipid peroxidation further support the above findings. The significant inhibition of the activities of lactate dehydrogenase and adenosine triphosphatase shows the interference of monensin with the normal energy supply in spermatogenesis. Moreover, the significant increase in the activities of acid phosphatase and thiamine pyrophosphatase demonstrates the interference of monensin with the Golgi-lysosomal complex of the rat testis. Induced DNA fragmentation indicates towards the impact of monensin on the DNA integrity and apoptosis. Further studies are needed to understand the important molecular mechanisms responsible for these effects.
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PMID:Effect of monensin on the enzymes of oxidative stress, thiamine pyrophosphatase and DNA integrity in rat testicular cells in vitro. 1690 1