Antagonistic action of uranyl nitrate on presynaptic neurotoxins from snake venoms.
Uranyl ion (UO2+2) antagonized the neuromuscular blocking action and phospholipase A2 activity of neurotoxins which act presynaptically [beta-bungarotoxin (beta-BuTX) and crotoxin] but did not affect the action of alpha-bungarotoxin and tetrodotoxin. On the basis of the kinetic analysis of the UO2+2 and strontium ion (Sr2+) antagonism of muscle paralysis induced by beta-bungarotoxin, it was found that they inhibited both the binding of the toxin and the steps following binding that brought about the neuromuscular blocking action of beta-bungarotoxin. Uranyl ion was about 50 times more potent than Sr2+ in antagonizing beta-bungarotoxin. High Ca2+ (10 mM) abolished but low Ca2+ (0.25-1.25 mM) medium enhanced the antagonizing action of UO2+2 and Sr2+. In low Ca2+ medium, UO2+2 markedly potentiated the amplitude of the twitch, subsequent addition of beta-bungarotoxin produced three phases of effects on the twitches, e.g. an initial depression, followed by the second facilitation and finally a rapid depression of twitches; however, approx. 70 min after beta-bungarotoxin the small twitches reached a steady state which persisted for more than 350 min. Therefore, it is evident that UO2+2 is the most potent antagonist of beta-bungarotoxin so far tested.
D000818:Animals; D002038:Bungarotoxins / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000494:pharmacology; D003439:Crotoxin / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D013324:Strontium / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000037:antagonists & inhibitors; D014501:Uranium / Q000494:pharmacology*; D014502:Uranyl Nitrate / Q000494:pharmacology*
D002038:Bungarotoxins; D014502:Uranyl Nitrate; D013779:Tetrodotoxin; D014501:Uranium; D003439:Crotoxin; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium; D013324:Strontium