Spider venoms inhibit L-glutamate binding to brain synaptic membrane receptors

The venoms from three spider species, Araneus gemma, Neoscona arabesca, and Argiope aurantia, were shown to inhibit the high-affinity, sodium-independent L-glutamate-binding sites in rat brain synaptic membranes. The same three venoms caused concentration-dependent inhibition of the activity of the glutamate-binding glycoprotein purified from rat brain synaptic membranes. The venom milked from the glands of Araneus gemma was the most active inhibitor of L-glutamate binding, causing 60-80% inhibition of both synaptic membrane and purified protein binding activity at 0.01 unit. The inhibitory activity of this venom was associated with a single protein peak obtained from gel permeation chromatography of the venom. Finally, the effect of the venom from Araneus gemma on the synaptic membrane glutamate-binding sites was slowly reversible. These observations indicate that the spider venoms have a direct effect on the recognition sites for L-glutamic acid in brain synaptic membranes and that these sites are related to the physiologic glutamate receptors.