Studies of sodium-potassium activated adenosine triphosphatase: VII—inhibition by erythrophleum alkaloids

Abstract

Erythrophleine and cassaine, two alkaloids occurring in the bark, leaves, and seeds of the genus Erythrophleum, were shown to be potent inhibitors of the digitalissensitive Na-K activated adenosine triphosphatase (Na-K ATPase) of rabbit brain, kidney, and ciliary body and cat choroid plexus. At 10 −4 M concentration, erythrophleine inhibited Na-K ATPase activity in all four tissues completely, while cassaine at 10 −4 M inhibited Na-K ATPase activity in the same tissues-an average of 86 per cent. Neither of these compounds caused significant inhibition of Mg-activated ATPase activity. The inhibition curves for erythrophleine and cassaine in rabbit brain had the same general shape as the curve for ouabain. The negative logarithms of the molar inhibitor concentration at which 50 per cent inhibition of Na-K ATPase activity occurs were 6.58 for erythrophleine, 5.96 for ouabain, and 5.28 for cassaine. All three compounds caused a stimulation of approximately 6 per cent at about 1 300 of their halfaximal inhibition concentrations. Increasing the K concentration in the assay medium from 0 to 40 mM caused 75 per cent reversal of the inhibition of rabbit brain Na-K ATPase by 5 × 10 −7 M erythrophleine as well as by 5 × 10 −7 M ouabain. No reversal was obtained of the Na-K ATPase inhibition by 10 −4 M erythrophleine and ouabain. It is concluded that the similarity of the effects of the erythrophleum alkaloids and the digitalis glycosides on the Na-K ATPase system may explain the remarkable similarity between these two groups of compounds in pharmacological properties and in inhibitory effects on active cation transport.