IBN-9727532 PI: EDWARDS Some animals can produce venom that includes not only slowly acting enzymes, but very rapidly acting neurotoxins, which are molecular compounds that have drastic effects on the signalling or transmission properties of nerve cells. These compounds may be used for prey capture, as in some snakes and spiders, or for defense, as in some insects. Recently it has been discovered that a potent rapid neurotoxicity remains in heat-denatured saliva of an insect called the assassin bug, which squirts this venomous saliva at predatory larger insects, causing rapid paralysis. This toxic activity appears to be from non-enzymatic peptides. This Small Grant for Exploratory Research is to isolate, purify and identify neuroactive components for comparison with known neuroactive peptides, and to establish their mode of action using pharmacological studies on insect nerve-muscle proparations. The working hypothesis is that the active components are peptides that act at the neuromuscular junction, or act to generally depolarize membranes by acting on specific channels or by creating membrane pores. This work opens a potentially large new area of research, because we know about some neurotoxic venoms from spiders and some from wasps and bees, but virtually nothing about other insect neurotoxins. The potential impact of this work in neuroscience is high because the few well-characterized known toxins have led to particularly useful information about the molecular structure of nerve cell membranes. This new venom may have novel molecular properties, and the amounts of readily collectable venom are far greater than for other insect or spider toxins, which could lead to an inexpensive commercial source for pharmacology. The impact of this work in ecology is also likely to be high because it will open questions about molecular evolution of insect venoms as well as evolutionary development of insect defense strategies.
