INHIBITION BY VANADIUM OF SODIUM AND POTASSIUM DEPENDENT ADENOSINE-TRIPHOSPHATASE DERIVED FROM ANIMAL AND HUMAN TISSUES

Abstract

Inhibition of ATPase by vanadium pentoxide [dissolved in H2O or in NaOH solution] was studied in microsomal fractions and tissue homogenates of kidney, brain and heart of several species, including humans [kidney only]. In some preparations V was the most potent inhibitor of Na+ + K+ ATPase activity so far reported. Concentrations of V causing 50% inhibition of Na+ + K+ ATPase activity ranged 6 .times. 10-8-5 .times. 10-7 M in microsomal fractions and 2 .times. 10-7- 1 .times. 10-6 M in tissue homogenates. Renal and cardiac enzymes were more sensitive to V than the brain enzyme, a phenomenon independent of enzyme specific activity. The enzyme in tissue homogenates was more resistant to V than the microsomal enzyme derived from the same tissues, suggesting a presence in tissues of protective agents. Mg2+ ATPase, which contaminated the enzyme preparations to a variable degree, was 1000-10,000 .times. more resistant to V than was Na+ + K+ ATPase. More detailed studies on the mechanism of inhibition were performed with dog and human kidney enzymes. The reversible nature of the inhibition was suggested by the fact that fractional inactivation of Na+ + K+ ATPase by V was independent of enzyme protein concentrations. The inhibitory effect was reduced by Na+ and increased by K+ or Mg2+. ATP alone, but not MgATP, antagonized the inhibition. This could mean that V inhibits the Na+ + K+ ATPase at the site activated by Na+, and that ATP protects the enzyme either by binding V or by competing for a mutual receptor on the enzyme. The inhibition was reduced by bovine serum albumin, probably binding V. The inhibition was also diminished by reducing agents, ascorbic acid and citric acid.