ラット及びウサギ脳Na, K-ATPase活性に対するbufadienolidesの作用

Na, K-ATPase

北海道歯学会

北海道歯学雑誌

The use of toad venom in Chinese medicine includes approximately 100 kinds of bufadienolides. Bufadienolides are cardiotonic steroids similar to the digitalis which is a heart failure therapeutic drug, and show inhibition of the Na, K-ATPase activity, but there are few reports. This study was carried out for the purpose of determining the effects of bufadienolides on Na, K-ATPase and its mechanism. We examined the effects of bufalin, cinobufagin, cinobufotalin, and ouabain, one of digitalis-like substances, on Na, K-ATPase activity purified from rabbit and rat brains. Bufadienolides and ouabain approximately demonstrated complete inhibition of rabbit and rat brain-derived Na, K-ATPase activity. The 50 percent inhibitory concentrations for both Na, K-ATPase activites were 290 and 260 nM for ouabain, 40 and 20 nM for bufalin, 230 and 90 nM for cinobufagin and 300 and 150 nM for cinobufotalin. Excluding cinobufotalin for rabbit brain Na, K-ATPase, bufadienolides showed stronger inhibitory effect than ouabain, specific inhibitor of Na, K-ATPase, and bufalin showed particularly strong effects. It was suggested that rat brain Na, K-ATPase was more susceptible to the cardiotonic steroid than rabbit brain. We then examined the effects of ouabain, bufalin, cinobufagin, cinobufotalin on Na+, K+, Mg2+ and ATP concentration-dependency of rabbit and rat brain Na, K-ATPase activity. Ouabain and bufadienolides increased the affinity for Na+, Mg2+ and ATP of Na, K-ATPase activity, and reduced affinity for K+. These results suggest that bufalin, cinobufagin, cinobufotalin inhibit Na, K-ATPase by a similar mechanism of ouabain. In other words, cardiotonic action and diuretic effects of toad venom are based on the inhibitory effect of Na, K-ATPase similar to digitalis.