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

Abstract

The effect of AlCl3 on the (Na+ /K+)ATPase activity of freeze-thawed synaptosomes, isolated from rat brain cortex, has been studied. The AlCl3 action on the enzyme hydrolytic activity was examined using in vitro and in vivo approaches. Following exposure to AlCl3 using both in vitro (synaptosomes incubated in the presence of AlCl3 for 5 min) and in vivo (synaptosomes isolated from rats that received 0.03 g AlCl3/day for 4 months) approaches, the (Na+/K+)ATPase activity was inhibited in a concentration-dependent way. The maximal inhibitory effect (similar to60%) was observed in the presence of a AlCl3 concentration >75 muM and at non-limiting ATP concentrations. Conversely, AlCl3 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 AlCl3-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. (C) 2003 Elsevier Inc. All rights reserved.