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.
Bougis
P E
PE
Université d'Aix-Marseille II, Faculté de Médecine Nord, France.
Khélif
A
A
Rochat
H
H
D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology*; D004546:Elapid Venoms / Q000302:isolation & purification / Q000494:pharmacology*; D004557:Electric Organ / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008962:Models, Theoretical; D009206:Myocardium / Q000201:enzymology; D010741:Phospholipases A / Q000302:isolation & purification / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013574:Synaptosomes / Q000201:enzymology; D014101:Torpedo
D004546:Elapid Venoms; D007527:Isoenzymes; D010741:Phospholipases A; D054467:Phospholipases A2; D000254:Sodium-Potassium-Exchanging ATPase