The inhibitory effect of aluminium on the (Na +/K +)ATPase activity of rat brain cortex synaptosomes

• Published in: Journal of inorganic biochemistry 2003-09, Vol.97 (1), p.143-150
• Main Authors: Silva, Virgı́lia S, Gonçalves, Paula P
• Format: Article
• Language: English
• Subjects: (Na +/K +)ATPase; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - metabolism; Aluminium; Aluminum - chemistry; Aluminum - pharmacology; Animals; Brain cortex; Cell Membrane - drug effects; Cell Membrane - metabolism; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - enzymology; Cerebral Cortex - metabolism; Computer Simulation; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Kinetics; Magnesium - chemistry; Magnesium - pharmacology; Male; Ouabain - pharmacology; Rat; Rats; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors; Substrate Specificity; Sulfhydryl Compounds - analysis; Synaptosome; Synaptosomes - chemistry; Synaptosomes - drug effects; Synaptosomes - enzymology; Synaptosomes - metabolism; Uridine Triphosphate - metabolism
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/S0162-0134(03)00257-5

The effect of AlCl 3 on the (Na +/K +)ATPase activity of freeze–thawed synaptosomes, isolated from rat brain cortex, has been studied. The AlCl 3 action on the enzyme hydrolytic activity was examined using in vitro and in vivo approaches. Following exposure to AlCl 3 using both in vitro (synaptosomes incubated in the presence of AlCl 3 for 5 min) and in vivo (synaptosomes isolated from rats that received 0.03 g AlCl 3/day for 4 months) approaches, the (Na +/K +)ATPase activity was inhibited in a concentration-dependent way. The maximal inhibitory effect (∼60%) was observed in the presence of a AlCl 3 concentration >75 μM and at non-limiting ATP concentrations. Conversely, AlCl 3 did not inhibit the enzyme activity when UTP was used as substrate instead of ATP. Analysis of the substrate dependence of membrane-bound (Na +/K +)ATPase by a computer simulation model suggests that the AlCl 3-induced inhibitory effect is characterised by a reduction of the rate-limiting step velocity of the reaction cycle. Moreover, it seems that aluminium can induce impairment of the interprotomeric interaction within the oligomeric ensemble of membrane-bound (Na +/K +)ATPase. In fact, this effect was accompanied by a slight, but significant, decrease of readily accessible SH groups, which are involved in the maintenance of the membrane-bound (Na +/K +)ATPase oligomeric structure. In conclusion, during exposure to aluminium, reduction of the activation of membrane-bound (Na +/K +)ATPase by high ATP concentrations occurs, which results in a partial inhibition of the enzyme.