Abstract
1.
1. The effects of bretylium on myocardial Mg
2+-dependent, Na
+−K
+-ATPase (EC 3.6.1.3) activity were compared with those of ouabain in guinea-pig heart preparations.
2.
2. Both ouabain and bretylium inhibited microsomal Na
+−K
+-ATPase activity in a concentration-dependent fashion in the range of 0.01–100 and 1.0–4000 μM, respectively. The IC
50 values were 1.93 ± 0.27
μM for ouabain and 2.45 ± 0.17 mM for bretylium.
3.
3. In another set of experiments, the effects of bretylium on the enzyme activity were tested in combination with 2.5 or 5.0 μM ouabain.
4.
4. The combined effects of the two drugs resulted in a net reduction in the total inhibitory activities of the individual drugs, which became more marked the higher the bretylium concentration. This trend seems to suggest a competitive mode of interaction of the two drugs in their inhibitory actions on Na
+−K
+-ATPase activity.
5.
5. The results demonstrate therefore that bretylium is a potent inhibitor of ouabain-inhibited ATP hydrolysis by myocardial Na
+−K
+-ATPase. These actions may be pertinent with regard to some of its cardiac actions.