On the inhibition of [Na+,K+]-ATPases by the components of Naja mossambica mossambica venom: evidence for two distinct rat brain [Na+,K+]-ATPase activities.

We have compared the effects of highly purified preparations of cardiotoxins and phospholipases A2 from Naja mossambica mossambica venom on rat brain [Na+,K+]-ATPase activity. The results were the following: (i) micromolar concentrations of cardiotoxin preparations were required to inhibit [Na+,K+]-ATPase activity to the extent achieved by picomolar concentrations of phospholipases A2; i.e., the inhibitory effect of cardiotoxins appeared to be related to the contamination of the preparations by trace amounts of phospholipase A2; (ii) comparing phospholipases A2 from varied origins, a correlation was observed between [Na+,K+]-ATPase inhibition, isoelectric point, and toxicity for mice; (iii) when rat brain membranes were used, incubation for extended times with the most basic N. mossambica mossambica phospholipase A2 resulted in a biphasic [Na+,K+]-ATPase inhibition, suggesting that two distinct [Na+,K+]-ATPases were affected differentially. In contrast, incubation of rat brain membranes with either porcine pancreatic phospholipase A2, notexin, or beta-bungarotoxin and also incubation of erythrocyte membranes with the most basic N. mossambica mossambica phospholipase A2 produced monophasic [Na+,K+]-ATPase inhibitions. We discuss a possible specific action of toxic, basic phospholipase A2 on one of the [Na+,K+]-ATPase isoforms of excitable membranes.