Philanthotoxins: A review of the diversity of actions on synaptic transmission

Abstract

The venom of the wasp Philanthus triangulum causes paralysis in insects. Although the wasp stings its natural prey (the worker of the honeybee) in the direction of the thoracic ganglia, the venom affects synaptic transmission in both the insect CNS and the neuromuscular system. The venom contains two agonists, 0-acetylcholine and glutamate, and three antagonists of low molecular weight v-, y-and S-philanthotoxin). The fland S-toxins have been purified and chemically characterised (mol. wt 243 and 435, respectively). Their structures have, as yet, to be proved by synthesis.6-Philanthotoxin exerts a diversity of actions on synaptic transmission processes. In the plasma membrane of locust muscle fibres, the toxin blocks open cation channels, gated by both junctional and extrajunctional glutamate receptors. Once the channel has been blocked in a use-dependent way, unblocking seems to be semi-irreversible when the agonist activation is low. In locust muscle, this toxin also inhibits the glutamate uptake in nerve terminals and glial cells, but the uptake of 4-aminobutyric acid (GABA), into the common inhibitor and in the glia, is not affected by S-philanthotoxin. In the locust proctodeum, 6-philanthotoxin blocks glutamate-gated cation channels, leaving the proctolin-induced effects unaffected.In the sixth abdominal ganglion of the cockroach, 6-philanthotoxin causes a slowly reversible block of synaptic transmission, from the cercal nerve XI to a giant interneuron, without any change in resting membrane potential, and leaves the axonal excitability unaffected. On this neuron, iontophoretically evoked 0-acetylcholine potentials are more sensitive than excitatory postsynaptic potentials, indicating a postsynaptic effect. In the rat phrenic nerve-diaphragm, the toxin reduces the temperature-and voltage-sensitivity of the 0-acetylcholine receptor-activated cation channel and shortens the decay time of the miniature end-plate currents. In the hippocampus slice of the rat, 6-philanthotoxin inhibits the uptake of glutamate.fl-Philanthotoxin has no paralysing activity when injected into the honeybee worker. However, it potentiates the paralysing activity of y-and 6-philanthotoxins. In the isolated locust muscle, fl-philanthotoxin inhibits the recovery from desensitisation by glutamate. This toxin seems to be inactive in all the other systems mentioned above.It is suggested that the efficacy of the venom of this wasp arises from a synergistic action of the agonists and antagonists. In the insect CNS, the channel block by the 8-toxin may be facilitated by channel opening because of a high concentration of 0-acetylcholine, while in the skeletal muscle of insects, the channel block by the 8-toxin may be facilitated by the inhibition of re-uptake of glutamate. Moreover, this inhibition may cause desensitisation, which would be facilitated by the inhibition of the recovery from desensitisation caused by the fl-toxin."Based on a presentation at the symposium Neuropharmacology and pesticide action (Neurotox '85) on 31 March to 4 April ...