PRINCIPLES OF TOXICOLOGY - Biology East Borneo

17.7 ANIMAL VENOMS AND TOXINS 427could be at least partially achieved by reducing postsynaptic membrane responsiveness to ACh withnicotinic and muscarinic receptor antagonists. This potential method of treatment could supplementthe use of antivenins.Spiders generally poison their insect prey. Fortunately, vertebrate nervous system receptors arepharmacologically different enough from those of insects that most spider toxins are not very activeon humans. It also helps that we are so big and their normal prey and predators are so small!Nevertheless, several spiders are exceedingly dangerous. Black widow spiders (Latrodectus sp.) occurthroughout the world, so we shall consider them first. Their venom is primarily neurotoxic due to thepresence of a powerful protein toxin called alpha-latrotoxin (Table 17.1). This large protein enhancesneurotransmitter release from nerve terminals, and can even cause nerve terminal secretory vesicledepletion. Victims concurrently suffer from skeletal muscle spasms and autonomic overstimulation(causing sweating, salivation, nausea, and hypertension). Again, treatment is primarily based uponadministration of Latrodectus antivenin. Some relief from these symptoms can be achieved withcentrally acting muscle relaxants like diazepam, and autonomic overstimulation can be amelioratedwith muscarinic and/or adrenergic antagonists, depending on the symptoms.Brown recluse spider venom (Loxoceles sp.) acts in an entirely different way because its venomprimarily contains an enzyme, sphingomyelinase, which causes tissue damage. While this venom isless dangerous than black widow venom, it can cause significant tissue necrosis at the site of the bite.Although the bees, hornets, and wasps all belong to the order Hymenoptera, their venoms aredifferent. The most serious reactions to hymenopteran stings are of the immediate hypersensitivitytype and are due to an immune response from previous stings mediated by immunoglobulin E. Beevenom has been found to be an exceedingly rich mixture of enzymes and toxins. The primary enzymeof importance is phospholipase A, which acts synergistically with a peptide detergent called mellitin(named after the common honeybee Apis mellifera) to break down phospholipids in the plasmamembrane, thereby liberating prolytic fatty acids and lysolecithin. While mellitin can act alone todisrupt the cell membrane, its action is greatly facilitated by the presence of these phospholipidbreakdown products. Like many snake venoms, bee venom also contains the enzyme hyaluronidase,which breaks down connective tissue and thus facilitates the spreading of the venom from its site ofinjection. Bee venom also contains two peptide toxins, apamin and mast cell degranulating peptide,which respectively block calcium-activated and voltage-activated potassium channels.In contrast to bee venom, the wasp and hornet venoms primarily contain small peptides called kininswhich, like our endogenous bradykinin, have a triple action: stimulation of sensory nerve endingsresulting in neurogenic inflammation, increased capillary permeability, and relaxation of vascularsmooth muscle.Fire ants (Solenopsis) are quite abundant in the southeastern United States, and many people arestung each year. The venom contains piperidine alkaloids, which have been found to block the nicotinicreceptor ion channel. Protein constituents are thought to be at least partly responsible for the painfulsensation associated with the sting. Irritating pustules and some minor tissue necrosis may result at thesting, extending the period of discomfort to several days. The role that the alkaloids (called solenopsins)play in the inflammatory responses associated with fire ant stings is not entirely clear, but solenopsinsare known to cause histamine release from basophils.Mollusc Venoms and ToxinsThe molluscan exoskeleton provides considerable protection against predators but also limits mobility.This poses a problem for predatory snails. However, one group of gastropods called “cones” possessesa formidable harpoon-like venom apparatus for paralyzing its prey. Conus venom was extensivelyinvestigated in the 1990s. Almost all Conus toxins are peptides or small proteins. The venom is a virtualcocktail of ion channel modulators including nicotinic receptor antagonists (α-conotoxins), sodiumchannel blockers (µ-conotoxins), calcium channel blockers (ω-conotoxins), and glutamate channelblockers (conantokins). Only a relatively small fraction of the 300 known species of Conus are