The role of enzyme activity and charge properties on the presynaptic neurotoxicity and the contracture-inducing activity of snake venom phospholipases A2.
Two toxic phospholipases A2, caudoxin from Bitis caudalis venom and the basic phospholipase A2 from Naja nigricollis venom, were selected for a study of the contribution of enzyme activity and charge properties to the presynaptic neurotoxicity and the contracture-inducing activity of the enzyme. Reducing catalytic activity by lowering the incubation temperature or by substitution of Sr2+ for Ca2+ in the bathing medium causes a significant prolongation of the time to neuromuscular block by caudoxin, but does not change the contracture-inducing activity of Naja nigricollis basic phospholipase A2. In the chick muscle pretreated with heparin, the latter enzyme fails to evoke contracture, whereas the presynaptic neuromuscular blocking action of caudoxin remains little affected. Histidine-modified Naja nigricollis enzyme, which has lost 95% of its enzyme activity, retains considerable ability to induce contracture and to abolish indirectly evoked contraction, while lysine-methylated enzyme, which loses only 10% of its enzyme activity, almost completely loses its ability to evoke muscle contracture. It is concluded that enzyme activity is important for the presynaptic effects of caudoxin, but not for the contracture-inducing action of the Naja nigricollis enzyme. In the latter enzyme certain easily methylated lysine residues are critical for its ability to induce muscle contracture.
D000818:Animals; D002118:Calcium; D002384:Catalysis; D002645:Chickens; D003080:Cold Temperature; D006493:Heparin / Q000494:pharmacology; D006639:Histidine; D066298:In Vitro Techniques; D008239:Lysine; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D054467:Phospholipases A2; D013324:Strontium; D013329:Structure-Activity Relationship
D009466:Neuromuscular Blocking Agents; D006639:Histidine; D006493:Heparin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D008239:Lysine; D002118:Calcium; D013324:Strontium