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

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Silva VS, Goncalves PP

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

J Inorg Biochem. 2003 Sep 15;97(1):143-50.

PubMed ID

14507470 [ View in PubMed

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Abstract

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 (approximately 60%) was observed in the presence of a AlCl(3) concentration >75 microM 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aluminium	Sodium/potassium-transporting ATPase subunit alpha-1	Protein	Humans	Unknown	Binder	Details
Aluminium phosphate	Sodium/potassium-transporting ATPase subunit alpha-1	Protein	Humans	Unknown	Not Available	Details
Aluminum acetate	Sodium/potassium-transporting ATPase subunit alpha-1	Protein	Humans	Unknown	Not Available	Details