Bovine serum albumin does not completely block synaptosomal cholinergic activities of presynaptically acting snake venom phospholipase A2 enzymes.
Bovine serum albumin (BSA), which binds fatty acids, was used to test the contribution of free fatty acid to the presynaptic toxicity of phospholipase A2 (PLA2) enzymes. The effects of BSA on inhibition of [14C]choline uptake and stimulation of [14C]acetylcholine (ACh) release in synaptosomes by PLA2 enzymes that do not have a predominant presynaptic action at the neuromuscular junction (PS-) were compared with those on the cholinergic actions of PLA2 enzymes that do have a predominant presynaptic action at the neuromuscular junction (PS+). The inhibition of choline uptake by the Naja naja atra PLA2, a PS- PLA2, was completely antagonized by BSA (0.5%); whereas that by beta-bungarotoxin, a PS+ PLA2, was unaffected by BSA. The inhibition of choline uptake by two other PS+ PLA2 toxins (scutoxin and pseudexin) was partially antagonized by BSA. The effects of the PLA2 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- PLA2 enzymes (from Naja naja atra and Naja naja kaouthia snake venoms) was completely blocked by BSA; whereas that by beta-bungarotoxin was unaffected and that by scutoxin and pseudexin was only partially antagonized by BSA. The results suggest that the PS- PLA2 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+ PLA2 enzymes in synaptosomes.
Fletcher
J E
JE
Department of Anesthesiology, Hahnemann University, Philadelphia, PA 19102-1192, USA.
Storella
R J
RJ
Jiang
M S
MS
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002038:Bungarotoxins / Q000633:toxicity; D002794:Choline / Q000378:metabolism; D003964:Diaphragm / Q000294:innervation; D004546:Elapid Venoms / Q000201:enzymology / Q000633:toxicity; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010791:Phrenic Nerve; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D012910:Snake Venoms / Q000201:enzymology / Q000633:toxicity*; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology
D002038:Bungarotoxins; D004546:Elapid Venoms; C026235:Pseudechis venom; D012910:Snake Venoms; C068736:scutoxin A; D012710:Serum Albumin, Bovine; D010741:Phospholipases A; D054467:Phospholipases A2; D002794:Choline; D000109:Acetylcholine