Reversal of snake neurotoxin binding to mammalian acetylcholine receptor by specific antiserum

Abstract

Snake curaremimetic toxins are known to bind to the nicotinic acetylcholine receptor (AcChoR) [Changeux et al. (1970) Proc. Natl Acad. Sci. USA, 67, 1241-1247], thus blocking neuromuscular transmission, and producing respiratory failure in mammals. In the present paper we show that the toxic effects of Naja nigricollis toxin .alpha. to mammals can be efficiently reversed by toxin-.alpha.-specific antibodies. In vivo we observed that return to normal breathing in toxin-.alpha.-intoxicated and ventilated rats was 12 times faster after injection of specific antiserum or monoclonal antibody (M.alpha.1] as compared with control animals. Ex vivo we observed that return to normal contraction of a toxin-.alpha.-blocked phrenic nerve-hemidiaphragm preparation was 14 times more rapid after treatment with specific antiserum than after washings. In vitro we observed that antibodies accelerated the reversal of binding of [3H]toxin .alpha. to AcChoR prepared from rat diaphragm. The observation made in vitro furthermore indicates that antibodies are capable of destabilizing the [3H]toxin-AcChoR complex. A similar destabilization phenomenon occurs also in vivo, as inferred from measurements of receptor occupancy by [3H]toxin .alpha. in diaphragm of anaesthetized rats in the presence or absence of antibodies. The property of antibodies to reverse neurotoxin binding to AcChoR may be considered as a critical test for evaluation of the quality of a neurotoxin-specific antisera.