Microsomes were prepared from placentas of normotensive women and of patients suffering from pregnancy- induced hypertension (PIH). Activity of Na,K-ATPase (estimated as ATP hydrolysis) from the hypertensive tissue was lower than from tissue of normotensive women, even if the number of Na,K-ATPase molecules (monitored by anthroyl ouabain binding) was actually greater in the hypertensive tissue. The affinity of Na,K-ATPase for anthroyl ouabain was about four times higher in plasma membranes of hypertensives, indicating some structural change in the Na,K-ATPase or in its vicinity. Assuming the presence of an endogenous digitalis-like factor, the results suggest a simple way of explaining not only the lower Ma,K-ATPase activity in the placental membranes of hypertensives but also the different extent of enzyme inhibition in different tissues of PIH patients.
Rhythmic daily changes in the Na,K-ATPase activity have been previously described for rat kidney cortex, showing two peaks: at 0900 h and 2100 h, and two valleys: at 1500 h and 0100 h - 0300 h. The oscillations in Na,K-ATPase activity are produced by an inhibitor, which binds the enzyme and is present in the rat blood plasma at valley times and absent or at very low concentrations at peak times. Since it has been demonstrated that active Na+ extrusion from the cells of several tissues depends not only on the Na,K-ATPase but also on the ouabain-insensitive Na-ATPase, we studied the activity of this latter enzyme of several rat tissues, i.e., kidney cortex, small intestine, liver, heart and red blood cells along the day. None of these tissues showed any variation of their Na-ATPase activity along the day. Preincubation of kidney cortex homogenates obtained at 0900 h, with blood plasma drawn at 0900 h and 1500 h, did not modify the Na-ATPase activity. Our results indicate that the Na-ATPase activity does not oscillate along the day. These results are in agreement with the idea that the Na-ATPase could partially compensate the Na+ transport affected by oscillations of the Na,K-ATPase activity., A. Reyes ... [et al.]., and Obsahuje seznam literatury
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.