The effects of potassium homologs and cisplatin on Na, K-ATPase of rabbit brain

Abstract

In Na, K-ATPase reaction, Na⁺ is indispensable to the formation of phosphointermediate, and K⁺ promotes dephosphorylation of phosphointermediate. It is known that Li⁺, Rb⁺, and Cs⁺, which are homologs of K⁺ and NH₄⁺, have a similar action to that of K⁺, but the details are not well understood. In the current study we examined the effects of the homologs of K⁺ and NH₄⁺ on Na, K-ATPase reaction and hydrolysis of p-nirophenyl phosphate (p-NPP), a partial reaction of Na, K-ATPase, using Na, K-ATPase purified from rabbit brains. In addition, since some previous reports suggested that inhibition of Na, K-ATPase activity by cisplatin may be the cause of renal failure, we examined the effects of cisplatin on the Na, K-ATPase activity which was dependent on the homologs of K⁺ and NH₄⁺.
The homologs of K⁺ and NH₄⁺ promoted ATPase activity in the presence of Na⁺ and Mg²⁺, and the order of the promoting effect and the affinity was K⁺> NH₄⁺ = Cs⁺= Rb⁺ > Li⁺. As no additive promotion of ATPase activity was observed by the addition of any of these ions in the presence of K⁺, the effects of these ions were thought to be similar to that of K⁺.
All the ions except Li⁺ activated hydrolysis of p-NPP as partial reaction of Na, K-ATPase. On the other hand, Li⁺ showed a promoting effect, as Na⁺ does, on ATPase activity in the absence of K⁺, whereas other homologs of K⁺ and NH₄⁺ did not. Cisplatin inhibited ATPase activity irrespective of the presence of K⁺, or homologs of K⁺ or NH₄⁺. Furthermore, cisplatin inhibited p-NPP hydrolysis activated by the homologs of K⁺ or NH₄⁺ and ATPase activity activated by Na⁺ or Li⁺.
These findings suggest that all the homologs of K⁺ and NH₄⁺ have an action on Na, K-ATPase activity, similar to that of K⁺, and only Li⁺ has both Na⁺- and K⁺- like effects, and that cisplatin inhibits ATPase and p-NPPase activities activated by the homologs of K⁺ and NH₄⁺.