AlF4- reversibly inhibits ‘P’-type cation-transport ATPases, possibly by interacting with the phosphate-binding site of the ATPase

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Abstract
The only known cellular action of AlF4- is to stimulate the G-proteins. The aim of the present work is to demonstrate that AlF4- also inhibits ''P''-type cation-transport ATPases. NaF plus AlCl3 completely and reversibly inhibits the activity of the purified (Na+ + K+)-ATPase (Na+ - and K+ -activated ATPase) and of the purified plasmalemmal (Ca2+ + Mg2+)-ATPase (Ca2+ -stimulated and Mg2+ -dependent ATPase). It partially inhibits the activity of the sarcoplasmic-reticulum (Ca2+ + Mg2+)-ATPase, whereas it does not affect the mitochondrial H+ -transporting ATPase. The inhibitory substances are neither F- nor Al3+ but rather fluoroaluminate complexes. Because AIF4- still inhibits the ATPase in the presence of guanosine 5'' -[.beta.-thio]diphosphate, and because guanosine 5''-[.beta..gamma.-imido]triphosphate does not inhibit the ATPase, it is unlikely that the inhibition could be due to the activation of an unknown G-protein. The time course of inhibition and the concentrations of NaF and AlCl3 required for this inhibition differ for the different ATPases. AIF4- inhibits the (Na+ + K-)ATPase and the plasmalemmal (Ca2+ + Mg2+)-ATPase noncompetitively with respect to ATP and to their respective cationic substrates, Na+ and Ca2+. AlF4- probably binds to the phosphate-binding site of the ATPase, as the Ki for inhibition of the (Na+ + K+)-ATPase and of the plasmalemmal (Ca2+ + Mg2+)-ATPase is shifted in the presence of respectively 5 and 50 mM-Pi to higher concentrations of NaF. Moreover, AlF4- inhibits the K+-activated p-nitrophenylphosphatase of the (Na+ + K+)-ATPase competitively with respect to p-nitrophenyl phosphate. This AlF4- -induced inhibition of ''P'' -type cation-transport ATPases warns us against explaining all the effects of AlF4- on intact cells by an activation of G-proteins.

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