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

The antitumor antibiotic Adriamycin is a potent inhibitor of the sodium-potassium-activated adenosine triphosphatase of native heart microsomes. Adriamycin also inhibits potassium transport (although not sodium transport) in slices of kidney cortex. The effects on both the adenosine triphosphatase and ion transport are markedly reduced by Ca2+, probably by chelation of this metal by Adriamycin. These effects could provide a basis for explaining the Adriamycin cardiotoxicity as a digitalis-type toxicity.
 ...
PMID:Inhibition of sodium-potassium-activated adenosine 5'-triphosphatase and ion transport by adriamycin. 21 83

Adriamycin ws tested as a possible inhibitor of cardiac sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase). At concentrations of 10(-4) M and lower, Adriamycin had no effect upon either ouabain-sensitive (Na-K-ATPase) or ouabain-insensitive adenosine triphosphatase activity in homogenates and microsomal fractions of cardiac tissue from several different species. Adriamycin inhibited adenosine triphosphatase activity at a concentration of 10(-3) M, but this was due to the inhibition of ouabain-insensitive adenosine triphosphatase rather than to inhibition of Na-K-ATPase. Under no condition was an inhibition of Na-K-ATPase activity by Adriamycin observed. These conditions included preincubation of the enzyme with Adriamycin, chelation of Ca2+, addition of reduced nicotinamide adenine dinucleotide phosphate, and variation of buffer and pH. It was concluded that Na-K-ATPase is not a likely site of Adriamycin-induced cardiotoxicity.
 ...
PMID:Cardiac sodium, potassium-adenosine triphosphatase as a possible site of adriamycin-induced cardiotoxicity. 625 69

Ouabain (OUA) inhibited 86Rb uptake (50% inhibitory concentration = 0.8 X 10(-4) M) over concentration ranges close to those at which it caused a reversible cytotoxicity (50% lethal dose = 2.5 X 10(-4) M) in growing wild-type C3H/10T1/2 cells. On the other hand, Adriamycin (ADM) inhibited 86Rb uptake (50% inhibitory concentration = 2 X 10(-3) M) but at concentrations 10(4)-fold higher than those causing irreversible cytotoxicity in growing wild-type cells (50% lethal dose = 3 X 10(-8) M). While OUA inhibited 86Rb uptake more in wild-type cells than in a OUA-resistant mutant, ADM inhibited 86Rb uptake to the same extent in confluent wild-type and OUA-resistant cells. Further, three OUA-resistant mutants were not cross-resistant to ADM- or daunomycin (DM)-induced cytotoxicity during log phase or to ADM-induced cytotoxicity at confluence. In addition, ADM, DM, or 5-iminodaunomycin did not displace the cardiac glycosides digoxin or digitoxin from their respective antibody complexes. The order of potency of anthracycline derivatives in inhibiting 86Rb uptake in confluent wild-type cells was the same as their order of inhibiting the growth of wild-type cells and in detaching confluent wild-type cells (DM > ADM > 5-iminodaunomycin) but did not correlate with their cardiotoxic potentials (ADM > DM > 5-iminodaunomycin). Therefore, in this model system, ADM cytotoxicity is mediated differently from OUA cytotoxicity. Further, we find no biological evidence consistent withADM binding to the OUA site on the cell surface (Na+-K+) adenosine triphosphatase and therefore no evidence in this model system that ADM cardiotoxicity could be a digitalis-type toxicity per se.
 ...
PMID:Comparison of adriamycin- and ouabain-induced cytotoxicity and inhibition of 86rubidium transport in wild-type and ouabain-resistant C3H/10T1/2 mouse fibroblasts. 743 92