The interaction between the presynaptic phospholipase neurotoxins beta-bungarotoxin and crotoxin and mixed detergent-phosphatidylcholine micelles. A comparison with non-neurotoxic snake venom phospholipases A2.
Certain phospholipase A2 enzymes (E.C.3.1.1.4) selectively inhibit neurotransmitter release from cholinergic nerve terminals. Both specific acceptor proteins and the physical state of nerve terminal phospholipids have been implicated in studies of the mechanism of phospholipase neurotoxin action. Here we have examined the effects of charge on a micellar phospholipid substrate by comparing the enzyme activity and binding of two neurotoxic phospholipases (beta-bungarotoxin and crotoxin) with other non-neurotoxic phospholipases. This has been achieved by altering either the phospholipid or the ionic charge of the detergent in the mixed phospholipid micelle. The neurotoxic phospholipases were only active on negatively charged micelles, whereas the non-neurotoxic enzymes were equally active in hydrolyzing neutral micelles. This distinction was also reflected in binding studies; the non-neurotoxic phospholipases bound to both types of substrate, whereas beta-bungarotoxin and crotoxin selectively bound to negatively charged micellar structures. These experiments suggest that, in addition to the existence of any specific acceptor proteins, neurotoxin binding is also governed by the charge on the lipid phase of the nerve terminal membrane.
D002038:Bungarotoxins / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism; D003435:Crotalid Venoms / Q000378:metabolism*; D003439:Crotoxin / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology*; D008563:Membrane Lipids / Q000378:metabolism; D008823:Micelles; D010713:Phosphatidylcholines; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013501:Surface-Active Agents / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
D002038:Bungarotoxins; D003435:Crotalid Venoms; D003902:Detergents; D008563:Membrane Lipids; D008823:Micelles; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D003439:Crotoxin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2