Differences in pharmacological actions between beta-bungarotoxin and other neurotoxic phospholipases A2 purified from snake venoms

Abstract

Five highly toxic phospholipases A2 (PLAs) (beta-bungarotoxin, caudoxin, Mojave toxin, notexin and a basic PLA from Naja nigricollis venom) were compared for their pharmacological actions. In the chick biventer cervicis nerve-muscle preparation, all PLA toxins except beta-bungarotoxin (beta-BuTX) inhibited the postsynaptic acetylcholine response and induced contracture of the muscle at a high concentration. Indirect hemolytic activity was found in all PLA toxins and some of the toxins (Naja nigricollis basic PLA and Mojave toxin) even showed a potent direct hemolytic action, while beta-BuTX was devoid of both direct and indirect hemolytic activities on the guinea-pig erythrocytes. All PLA toxins except beta-BuTX caused an increase in muscle tone in the guinea-pig ileum at a concentration as low as 0.05 microgram/ml, and an increase in the contractile force in the guinea-pig atrium at a concentration of 1.0 microgram/ml. In contrast, beta-BuTX had no stimulant effect at concentrations up to 10 micrograms/ml. On the cultured cells, beta-BuTX suppressed the proliferation of neuroblastoma cells, but did not cause lysis of non-neuronal cells of the rat brain. However, beta-BuTX uniquely maintained a high population of viable cells in the neuroblastoma cell cultures. From these results it was concluded that beta-BuTX is the most specific presynaptic neurotoxin among the PLA toxins so far tested.