title: AlF4- reversibly inhibits 'P'-type cation-transport ATPases, possibly by interacting with the phosphate-binding site of the ATPase.
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 AlF4- 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. AlF4- 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.
authors.affiliation: Department of Physiology, Catholic University of Leuven, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Missiaen
authors.forename: F
authors.initials: F
authors.lastname: Wuytack
authors.forename: H
authors.initials: H
authors.lastname: De Smedt
authors.forename: M
authors.initials: M
authors.lastname: Vrolix
authors.forename: R
authors.initials: R
authors.lastname: Casteels
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000535:Aluminum / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001608:Beryllium / Q000494:pharmacology; D001665:Binding Sites; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000201:enzymology; D002712:Chlorides / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D009596:Nitrophenols / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D007527:Isoenzymes; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D010710:Phosphates; D013873:Thionucleotides; C034883:guanosine 5'-O-(2-thiotriphosphate); D015636:Magnesium Chloride; C008644:nitrophenylphosphate; D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000077410:Aluminum Chloride; C032776:beryllium chloride; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D000535:Aluminum; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium; D003676:Deferoxamine; D001608:Beryllium; D005459:Fluorides; C032311:aluminum fluoride