Effects of beta-bungarotoxin and phospholipase A2 from Naja naja atra snake venom on ATPase activities of synaptic membranes from rat cerebral cortex.
Non-neurotoxic phospholipase A2 of Formosan cobra venom possessed higher hydrolytic activity on phosphatidylcholine vesicles and also had higher inhibitory action on Na+-K+-ATpase and Mg2+-ATPase of the rat synaptic membrane than neurotoxic beta-bungarotoxin of Formosan Krait Venom. Na+-K+-ATPase was more susceptible than Mg2+-ATPase to the inhibitory action of toxins, especially in the presence of Triton X-100. The inhibition of ATPases by toxins followed the Michaelis-Menton equation. It is interesting that various phospholipids and ions influenced phospholipase A2 and beta-bungarotoxin inhibition of ATPases. Sphingomyelin antagonized phospholipase A4 more profoundly than beta-bungarotoxin, while egg lecithin had the reverse effect. Both phosphatidylethanolamine and phosphatidylserine protected Na+-K+-ATPase from the inhibitory action of phospholipase A2 but not that of beta-bungarotoxin. High K+ (30 mM) did not affect, while Ca2+ (0.2 mM) decreased, the inhibitory action of phospholipase A2 on Na+-K+-ATPase; in contrast, high K+ reversed, and Ca2+ increased, that of beta-bungarotoxin. These findings imply that phospholipase A2 and beta-bungarotoxin may have different substrate specificities and prefer different conformational states of the membrane for binding. This may explain, at least in part, why beta-bungarotoxin is neurotoxic, while phospholipase A2 is not.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D002038:Bungarotoxins / Q000633:toxicity*; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000201:enzymology; D004546:Elapid Venoms / Q000633:toxicity*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010740:Phospholipases / Q000633:toxicity*; D010741:Phospholipases A / Q000633:toxicity*; D054467:Phospholipases A2; D010743:Phospholipids / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012911:Snakes; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013570:Synaptic Membranes / Q000201:enzymology*
D002038:Bungarotoxins; D004546:Elapid Venoms; D010743:Phospholipids; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium