Site of action of caudoxin, a neurotoxic phospholipase A2 from the horned puff adder (Bitis caudalis) venom.

Caudoxin, a single-chain phospholipase A2 isolated from the venom of Bitis caudalis is a toxic polypeptide with a formula weight of 13,332 dalton. The LD50 in mice (i.p.) was 0.18 (0.15-0.22) mg/kg. In the chick biventer cervicis muscle preparation the toxin (1-10 micrograms per ml) caused complete neuromuscular blockade without affecting the response of the muscle to acetylcholine. In the mouse phrenic nerve-diaphragm preparation, the toxin abolished the indirectly elicited contraction without inhibiting that evoked directly. When this preparation was bathed in a low calcium (0.6 mM) medium, the toxin induced a triphasic change in the indirectly evoked contractions: an immediate initial inhibition followed by augmentation and then a second phase of inhibition leading to irreversible neuromuscular blockade. Electrophysiological studies in the same preparation showed a similar triphasic change in the quantal content of endplate potentials. The frequency of miniature endplate potentials first increased and then decreased, while the resting membrane potential was not significantly decreased by the toxin. Histological study showed that the toxin caused local myonecrosis only at a higher dose (2 mg/kg mouse). It is concluded that caudoxin produced a neuromuscular block by acting selectively on a presynaptic site. However, the site of binding appears to be different from that of beta-bungarotoxin since combination of the toxin with beta-bungarotoxin caused potentiation of its neuromuscular blocking action rather than addition.