Bovine serum albumin does not completely block synaptosomal cholinergic activities of presynaptically acting snake venom phospholipase A 2 enzymes

Abstract

Bovine serum albumin (BSA), which binds fatty acids, was used to test the contribution of free fatty acid to the presynaptic toxicity of phospholipase A 2 (PLA 2) enzymes. The effects of BSA on inhibition of [ 14C]choline uptake and stimulation of [ 14C]acetylcholine (ACh) release in synaptosomes by PLA 2 enzymes that do not have a predominant presynaptic action at the neuromuscular junction (PS−) were compared with those on the cholinergic actions of PLA 2 enzymes that do have a predominant presynaptic action at the neuromuscular junction (PS+). The inhibition of choline uptake by the Naja naja atra PLA 2, a PS− PLA 2, was completely antagonized by BSA (0.5%); whereas that by β-bungarotoxin, a PS+ PLA 2, was unaffected by BSA. The inhibition of choline uptake by two other PS+ PLA 2 toxins (scutoxin and pseudexin) was partially antagonized by BSA. The effects of the PLA 2 enzymes were antagonized in the same manner by BSA whether on Na +-dependent or on Na +-independent choline uptake. Likewise, the stimulation of ACh release by two PS− PLA 2 enzymes (from Naja naja atra and Naja naja kaouthia snake venoms) was completely blocked by BSA; whereas that by β-bungarotoxin was unaffected and that by scutoxin and pseudexin was only partially antagonized by BSA. The results suggest that the PS− PLA 2 enzymes are completely dependent on fatty acid production for their cholinergic toxicity and that BSA can be used to investigate further the neurotoxic mechanisms of PS+ PLA 2 enzymes in synaptosomes.