Aluminum-induced alterations in [3H]ouabain binding and ATP hydrolysis catalyzed by the rat brain synaptosomal (Na(+)+K+)-ATPase.
The (Na(+)+K+)-ATPase is responsible for maintenance of the ionic milieu of cells. The objective of this study is to investigate the effect of aluminum, an ion implicated in several neurological disorders, on ATP hydrolysis catalyzed by the rat brain synaptosomal (Na(+)+K+)-ATPase and on the binding of [3H]ouabain to this enzyme. AlCl3 (25-100 microM) inhibits the phosphatase activity of the (Na(+)+K+)-ATPase in a dose-dependent manner. AlCl3 appears to act as a reversible, noncompetitive inhibitor of (Na(+)+K+)-ATPase activity by decreasing the maximum velocity of the enzyme without significantly affecting the apparent dissociation constant with respect to ATP. AlCl3 may affect Mg2+ sites on the (Na(+)+K+)-ATPase but does not appear to interact with Na+ or K+ sites on the enzyme. In contrast to this inhibitory effect on the phosphatase function of the enzyme, AlCl3 (1-100 microM) stimulates the binding of [3H]ouabain to the (Na(+)+K+)-ATPase. This effect is due to an increase in the maximum [3H]ouabain binding capacity of the enzyme with no change in the [3H]ouabain binding affinity. These data support the hypothesis that AlCl3 may stabilize the phosphorylated form of the synaptosomal (Na(+)+K+)-ATPase which increases [3H]ouabain binding while inhibiting the phosphatase activity of the enzyme.
Caspers
M L
ML
Department of Chemistry, University of Detroit Mercy, MI 48219-0900.
Dow
M J
MJ
Fu
M J
MJ
Jacques
P S
PS
Kwaiser
T M
TM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D006868:Hydrolysis; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology*
D010042:Ouabain; D000255:Adenosine Triphosphate; D000535:Aluminum; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium