Involvement of Lipid Metabolism in the Action of Phospholipase A2 Neurotoxins

摘要

Presynaptically-acting neurotoxins (PSNTXs) from snake venom irreversiblystimulate acetylcholine (ACh) release from and inhibit choline uptake into synaptosomes, with rat synaptosomes affected by more toxins than those from mice. The inclusion of BSA in the incubation medium at the time of toxin exposure has allowed a clear distinction to be made between nonPSNTX phospholipases A2 (PLA2s) and the PSNTXs in synaptosome preparations. The stimulation of ACh release by scutoxin and pseudexin, but not by Beta-bungarotoxin (Beta-Butx), was antagonized only by neutralizing antibodies to pseudexin. The PSNTXs exhibit a pattern of phospholipid hydrolysis different from nonPSNTX PLA2s, as determined either by type of fatty acid liberated, or by the type of phospholipid hydrolyzed. This PLA2 activity may play a role in neurotoxicity. PSNTXs (Beta-Butx), cardiotoxins (CTXs), melittin and myotoxin alpha all cause Ca2+ release from the terminal cisternae of the sarcoplasmic reticulum through the Ca2+ release channel. Melittin and CTX, but not PSNTXs or myotoxin alpha, activate phospholipase C activity with no requirement for extracellular Ca2+. Presynaptic snake venom toxins, Phospholipase A2 toxins, Cardiotoxins, Lipids, Phospholipase C, Skeletal muscle, Synaptosomes, Cell culture, Beta-bungarotoxin, Scutoxin, RA I.