Inhibition by metals of a canine renal calcium, magnesium-activated adenosinetriphosphatase

A number of metals were examined for inhibition of a canine renal calcium, magnesium-activated adenosinetriphosphatase (Ca2+, Mg2+-ATPase). Of the 27 metals investigated, only compounds of mercury, silver, gold, and uranium demonstrated 50% inhibition of the enzyme at concentrations lower than 10(-4) M. The order of inhibitory potency was Hg greater than Ag greater than U greater than Au. Organic mercury (chlormerodrin, mersalyl, p-chloromercuribenzoate) was less potent than inorganic mercuric chloride, but organic gold sodium thiomalate was equipotent with inorganic gold chloride. The inhibition produced by each metal decreased parallel to the decrease in enzyme activity, seen as the source of enzyme moved from the outer cortex inward to the papilla of the kidney. The regions of highest activity showed the greatest inhibition by each metal, and inhibition decreased as the control activity of the tissue decreased. This variability of inhibition was not related to the protein content of the enzyme preparation. As the ATP concentration increased, the inhibition produced by U was reduced; if the Mg (but not the Ca concentration) was increased while the ATP concentration remained constant, the inhibition increased. Changes in the Ca, Mg, and ATP concentrations did not alter the inhibition produced by Hg, Ag, and Au.