Selective inhibition of brain Na,K-ATPase by drugs
Апстракт
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 GT GT promethazine GT verapamil GT = 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 concl...uded 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.
Кључне речи:
Na,K-ATPase / synaptosomes / verapamil / propranolol / promethazineИзвор:
Physiological Research, 2006, 55, 3, 325-338Колекције
Институција/група
VinčaTY - JOUR AU - Horvat, Anica AU - Momić, Tatjana AU - Banjac, Ana AU - Petrović S. AU - Nikezić, Gordana S. AU - Demajo, Miroslav PY - 2006 UR - https://vinar.vin.bg.ac.rs/handle/123456789/3040 AB - 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 GT GT promethazine GT verapamil GT = 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. T2 - Physiological Research T1 - Selective inhibition of brain Na,K-ATPase by drugs VL - 55 IS - 3 SP - 325 EP - 338 UR - https://hdl.handle.net/21.15107/rcub_vinar_3040 ER -
@article{ author = "Horvat, Anica and Momić, Tatjana and Banjac, Ana and Petrović S. and Nikezić, Gordana S. and Demajo, Miroslav", year = "2006", abstract = "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 GT GT promethazine GT verapamil GT = 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.", journal = "Physiological Research", title = "Selective inhibition of brain Na,K-ATPase by drugs", volume = "55", number = "3", pages = "325-338", url = "https://hdl.handle.net/21.15107/rcub_vinar_3040" }
Horvat, A., Momić, T., Banjac, A., Petrović S., Nikezić, G. S.,& Demajo, M.. (2006). Selective inhibition of brain Na,K-ATPase by drugs. in Physiological Research, 55(3), 325-338. https://hdl.handle.net/21.15107/rcub_vinar_3040
Horvat A, Momić T, Banjac A, Petrović S., Nikezić GS, Demajo M. Selective inhibition of brain Na,K-ATPase by drugs. in Physiological Research. 2006;55(3):325-338. https://hdl.handle.net/21.15107/rcub_vinar_3040 .
Horvat, Anica, Momić, Tatjana, Banjac, Ana, Petrović S., Nikezić, Gordana S., Demajo, Miroslav, "Selective inhibition of brain Na,K-ATPase by drugs" in Physiological Research, 55, no. 3 (2006):325-338, https://hdl.handle.net/21.15107/rcub_vinar_3040 .