Presynaptic effects of snake venom toxins which have phospholipase A2 activity (beta-bungarotoxin, taipoxin, crotoxin).
The presynaptic effects of beta-bungarotoxin, crotoxin and taipoxin were studied in the mouse phrenic nerve-diaphragm preparation (27 degrees C). The phospholipase A2 activity, assayed by pH-stat titration, was reduced to 4-10% at 27 degrees C compared with that at 37 degrees C. The late neuromuscular blocking activity was also reduced by more than three fold for all toxins. In contrast, the early biphasic response to the toxins, i.e. immediate depression followed by facilitation, was not delayed. The evoked quantal release of acetylcholine was enhanced by all toxins at low Ca2+-concentrations during the phase of facilitation, without an increase of the maximal release. At the late phase of treatment with beta-bungarotoxin and taipoxin, the curve relating the quantal contents of endplate potentials with Ca2+-concentration was shifted parallel to the right at low Ca2+, but marked depression of the maximal release occurred at high Ca2+. When diaminopyridine was added at the time of the late phase block by beta-bungarotoxin, the quantal release could still be enhanced at low Ca2+-concentrations, even beyond control; however, the maximal release was not simultaneously restored. It is concluded that the late phase block, but not the early biphasic response, is due to an enzymatic action and the release mechanism is abolished when the hydrolysis of membrane phospholipids proceeds to a certain critical level.
D000109:Acetylcholine / Q000378:metabolism; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000494:pharmacology*; D003439:Crotoxin / Q000494:pharmacology*; D004546:Elapid Venoms / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D010740:Phospholipases / Q000032:analysis*; D010741:Phospholipases A / Q000032:analysis*; D054467:Phospholipases A2; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013696:Temperature
D000631:Aminopyridines; D002038:Bungarotoxins; D003435:Crotalid Venoms; D004546:Elapid Venoms; D007473:Ion Channels; D017981:Receptors, Neurotransmitter; C015523:taipoxin; D003439:Crotoxin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000109:Acetylcholine