PRINCIPLES OF TOXICOLOGY - Biology East Borneo

424 PROPERTIES AND EFFECTS OF NATURAL TOXINS AND VENOMSFigure 17.6 The Eastern diamondback rattlesnake (Crotalus adamanteus) is one of the most dangerous pit vipers.On a weight basis its venom is not nearly as powerful as cobra or coral snake venom, but it compensates for thisby injecting a much larger quantity of venom with an efficient venom delivery apparatus.Cobra or sea snake envenomation often causes respiratory arrest before any signs of local tissue orsystemic cardiovascular damage are apparent. The major neurotoxin occurring in elapid andhydrophiid venoms is α-neurotoxin. This is a basic polypeptide of 65–80 amino acid residues thatis crosslinked with four or five disulfide bonds. The toxin acts as a competitive antagonist of theneurotransmitter acetylcholine (ACh) at the skeletal muscle neuromuscular junction. Unlike thenondepolarizing muscle relaxants used in surgery, which act at the same site, α-neurotoxin bindsvery tightly because its greater molecular size permits many contacts with the nicotinic receptor.In fact, a toxin found in the Taiwanese krait (Bungarus multicinctus), alpha-bungarotoxin, bindsessentially irreversibly to the skeletal muscle nicotinic receptor, preventing ACh from interactingwith its postsynaptic receptor. As if this potent neurotoxin were not sufficient to paralyze theskeletal muscle, this snake also makes a larger protein toxin called beta-bungarotoxin (Table 17.1),which inhibits the release of ACh from the motor nerve terminal; these two toxins, workingtogether in a synergistic fashion, can reduce the probability of neuromuscular transmission tozero. Besides the postsynaptic alpha-neurotoxic peptides, elapid venoms also generally containphospholipase A and a peptide called cardiotoxin, which is a cytolysin that tends to attack cardiacmyocardial cells. Cardiotoxin disrupts the bilayer structure of membrane lipids, and thereby makesthese lipids more accessible substrates for the phospholipase A.Coral snakes are the only new-world elapids. About 50 species have been described. In the UnitedStates there are only two species, but in central America and the northern parts of South America thereare many species. Coral snake bites are rarely as life-threatening as cobra bites because the volume ofvenom injected is usually quite small. Elapid snakes lack the fangs observed in the pit vipers, andtherefore, they must resort to a more lengthy chewing method of envenomation, which is not nearlyas efficient. The major danger for elapid snake envenomation victims is respiratory arrest due toblockade of neuromuscular transmission, and secondarily, cardiac systolic arrest due to the synergistic