Selective Inhibition of Brain
Na,K-ATPase by Drugs
A. HORVAT, T. MOMIĆ, A. BANJAC, S. PETROVIĆ, G.
NIKEZIĆ, M. DEMAJO
Laboratory for Molecular Biology and Endocrinology, “Vinča”
Institute of Nuclear Sciences, Belgrade, Serbia and Montenegro
Received August 27, 2004
Accepted July 18, 2005
On-line available August 5, 2005
The effect of drugs from the class of cardiac (methyldigoxin,
verapamil, propranolol), antiepileptic (carbamazepine), sedative
(diazepam) and antihistaminic (promethazine) drugs on
Na,K-ATPase activity of plasma membranes was studied in rat
brain synaptosomes. Methyldigoxin in a concentration of 0.1
mmol/l inhibits enzyme activity by 80 %. Verapamil, propranolol
and promethazine in concentrations of 20, 20 and 2 mmol/l
respectively, entirely inhibit the ATPase activity.
Carbamazepine and diazepam in concentrations of 0.02-60 mmol/l
have no effect on the activity of this enzyme. According to the
drug concentrations that inhibit 50 % of enzyme activity (IC50),
the potency can be listed in the following order: methyldigoxin
> > promethazine > verapamil ≥ propranolol. From the inhibition
of commercially available purified Na,K-ATPase isolated from
porcine cerebral cortex in the presence of chosen drugs, as well
as from kinetic studies on synaptosomal plasma membranes, it may
be concluded that the drugs inhibit enzyme activity, partly by
acting directly on the enzyme proteins. Propranolol, verapamil
and promethazine inhibitions acted in an uncompetitive manner.
The results suggest that these three drugs may contribute to
neurological dysfunctions and indicate the necessity to take
into consideration the side effects of the investigated drugs
during the treatment of various pathological conditions.
Na,K-ATPase • Synaptosomes • Verapamil • Propranolol •