CHARACTERISTICS OF INHIBITION OF HUMAN RENAL ADENOSINE TRIPHOSPHATASES BY CISPLATIN AND CHLOROPLATINIC ACID

  • 1 January 1984
    • journal article
    • research article
    • Vol. 68  (9) , 1135-1141
Abstract
Cisplatin and chloroplatinic acid were examined for in vitro inhibition of human renal microsomal adenosine triphosphatases activated by Na+ + K+ + Mg2+, Mg2+ and Ca2+. The concentrations of cisplatin to inhibit 50% of activity (150) were .apprx. 7 .times. 10-4 M for all enzymes studied; 150s of chloroplatinic acid were on the order of 10-5 M for Na+ + K+ + Mg2+ ATPase and Ca2+ ATPase and 10-7 M for Mg2+ ATPase in the presence of Na+ + K+ + ouabain. Inhibition of Na+ + K+ + Mg2+ ATPase by cisplatin or chloroplatinic acid was reversible and was not altered by varying Na+, K+ or Mg2+ concentration. ATP or MgATP increased inhibition by cisplatin but not by chloroplatinic acid. Acidic pH of 6.8 lowered inhibition by chloroplatinic acid but not by cisplatin. Cysteine, glutathione (-SH reagents), and ascorbic acid greatly reduced inhibition of all enzymes studied by chloroplatinic acid. In the case of cisplatin, -SH reagents had only a minimal protective effect but ascorbic acid somewhat increased inhibition. Methionine greatly increased inhibition by cisplatin but provided minimal protection in the case of chloroplatinic acid. Inhibition of renal Na+ + K+ ATPase may be associated with tubular damage, the inhibition of Na+ + K+ ATPase may be relevant to the mechanism of platinum toxicity.