Effects of polyamines on partial reactions of membrane (Na⁺ + K⁺)-ATPase

Spermine and spermidine inhibit the (Na⁺ + K⁺)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) reaction so that the effect increases as the ionic content due to Na⁺ and K⁺ in the reaction is reduced. Several other amines inhibit (Na⁺ + K⁺)-ATPase to varying degress and methylglyoxal-bis(guanylhydrazone) was the most potent inhibitor among those tested. The inhibition by polyamines of the ATPase is uncompetitive with respect to Mg²⁺ and ATP activation of the reaction. Various naturally occurring polyamines and other amines inhibited Na⁺ activation of (Na⁺ + K⁺)-ATPase as well as Na⁺-dependent phosphoenzyme formation in an apparently competitive manner with respect to Na⁺. Likewise, K⁺-activation of (Na⁺ + K⁺)-ATPase as well as K⁺-p-nitrophenyl phosphatase was inhibited in an apparently competitive manner with respect to K⁺. Both the cation charge and structure (e.g., aliphatic chain length) may contribute to the inhibitory effects of the amines; however, Na⁺ sites appear to be more sensitive to cation charge than the aliphatic chain length of the amine, whereas the opposite appears to be true for K⁺ sites. The results do not indicate a specific effect of polyamines on (Na⁺ + K⁺)-ATPase or its partial reactions.