beta-Bungarotoxin, a pre-synaptic toxin with enzymatic activity.

Abstract

ABSTRACT,5-Bungarotoxin, a pre-synaptic neurotoxin isolated from the venom of the snake Bungarus multicinctus, has been shown to modify release of neurotransmitter at the neuromuscular junction. In this communication, we demonstrate that jP-bungarotoxin is a potent phospholipase A2 (phosphatide 2-acyl hydrolase, EC 3.1.1.4), comparable in activity with purified phospholipase enzymes from Naja naja and Vipera russeii. The phospholipase activity of fl-bungarotoxin requires calcium and is stimulated by deoxycholate. When strontium replaces calcium no phospholipase activity is detected. Since neuromuscufar transmission is not blocked when calcium is re laced by strontium, it was possible to examine the effects of the toxin on neuromuscular transmission in the presence of strontium. Under these conditions, when the phospholipase activity should be inhibited, the toxin has little or no effect on neuromuscular transmission. If fl-bungarotoxin owes its toxicity in part to its enzymatic activity, then it must be placed in a different class from those toxins which produce their effect by binding passively to an appropriate receptor.

The Mode of Action at the Mouse Neuromuscular Junction of the Phospholipase A‐crotapotin Complex Isolated From Venom of the South American Rattlesnake

“…Although the role of catalytic activity in the neurotoxic action of notexin has been contested (Halpert, Eaker & Karlsson, 1976) it is strongly implicated in the action of G-bungarotoxin (Abe, Limbrick & Miledi, 1976). In a study of the ionic requirements for enzymatic and toxic activities off,-bungarotoxin, replacement of Ca by Sr was shown to reduce both these activities of the molecule in parallel (Strong, Goerke, Oberg & Kelly, 1976). The PhA activity was therefore considered a necessary but insufficient causal factor alone.…”

Morphometric analysis of the developing, murine aneural soleus muscle

“…However, more recent studies suggest that some secondary myotubes form in the absence of nerve (Fredette and Landmesser, 1991). While it is possible to surgically denervate developing birds in ovo (Butler et al, 1982;Phillips and Bennett, 19841, studies of the effects of denervation on mammalian fetal muscle have involved the injection of rat fetuses with p-bungarotoxin (Harris, 1981;Ross et al, 1987;Harris et al, 19891, a toxin that binds presynaptically to cholinergic nerve terminals (Chang and Lee, 1963) and that is neurotoxic because of its phospholipase activity (Strong et al, 1976). Although early studies using this protocol (Harris, 1981;Ross et al, 1987;Harris et al, 1989) have suggested that primary myotube formation in mammals is nerve independent while secondary myotube formation is nerve dependent, a recent immunohistochemical study (Condon et al, 1990) has provided evidence that some secondary myotubes are present in most hindlimb muscles of p-bungarotoxin-treated rat fetuses.…”

Identification by cross-linking of a beta-bungarotoxin binding polypeptide in chick brain membranes.

“…of 13 000 and 7500 which are linked by S-S bridges (Howard and Gundersen, 1980;Kelly and Brown, 1974;Wernicke et al, 1975). In common with other snake venom neurotoxins, the larger subunit carries a Ca2+-dependent phospholipase A2 activity (Strong et al, 1976 cross-linked membranes were subjected to SDS-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. As shown in Figure 1, Figure 2A); (ii) SDS-PAGE of cross-linked membrane samples on a 5-10% gradient gel also gave only one labeled band of apparent mol.…”