Suramin inhibits the early effects of PLA

Several phospholipase A 2 (PLA 2 ) neurotoxins from snake venoms can affect acetylcholine release at the neuromuscular junction. In isolated nerve-muscle preparations three distinct phases have been described for this phenomenon: An initial transient decrease in twitch tension; a second facilitatory phase during which twitch height is greater than control twitch height; and the last phase which causes a reduction in twitch height that fi nally results in paralysis. Suramin has been reported to inhibit the toxic effects of β-bungarotoxin and another PLA 2 neurotoxin, crotoxin in vitro and in vivo. We have further examined the effects of suramin on the three phases of the effects of the presynaptic PLA 2 neurotoxins β-bungarotoxin, taipoxin and ammodytoxin on mouse phrenic nerve-hemidiaphragm preparations. When preparations were pre-treated with suramin (0.3mM), the early biphasic effects (depression followed by facilitation) were abolished, and the time taken for fi nal blockade induced by β-bungarotoxin, taipoxin and ammodytoxin A was signifi cantly prolonged. In contrast, suramin did not signifi cantly affect the facilitation induced by the potassium channel blocking toxin dendrotoxin I when applied under the same conditions. In addition, application of 0.3mM suramin did not prevent the facilitatory actions of 3,4-diaminopyridine (3,4-DAP) and tetraethylammonium chloride (TEA). Overall, the mechanism whereby suramin reduces the effects of PLA 2 neurotoxins remains elusive. Since suramin reduces both enzyme-dependent and enzyme-independent effects of the toxins, suramin is not acting as a simple enzyme inhibitor. Furthermore, the observation that suramin does not affect actions of standard K channel blockers suggests that suramin does not stabilise nerve terminals.