Inhibition by vanadium of sodium and potassium dependent adenosinetriphosphatase derived from animal and human tissues

Inhibition of adenosinetriphosphatase (ATPase) by vanadium pentoxide (dissolved in water or in sodium hydroxide solution) was studied in microsomal fractions and tissue homogenates of kidney, brain, and heart of several species, including humans (kidney only). In some preparations vanadium was found to be the most potent inhibitor of Na+ + K+ATPase activity so far reported. Concentrations of vanadium causing 50 percent inhibition of Na+ + K+ATPase activity ranged from 6 x 10(-8) to 5 x 10(-7) M in microsomal fractions and from 2 x 10(-7) to 1 x 10(-6) M in tissue homogenates. Renal and cardiac enzymes were more sensitive to vanadium than the brain enzyme, a phenomenon independent of enzyme specific activity. The enzyme in tissue homogenates was more resistant to vanadium 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 1,000-10,000 times more resistant to vanadium 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 vanadium 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 vanadium inhibits the Na+ + K+ATPase at the site activated by Na+, and that ATP protects the enzyme either by binding vanadium or by competing for a mutual receptor on the enzyme. The inhibition was reduced by bovine serum albumin, probably binding vanadium. The inhibition was also diminished by reducing agents, ascorbic acid and citric acid.