Molecular action mechanism of spider toxin on glutamate receptor: role of 2,4-dihydroxyphenylacetic acid in toxin molecule.

Joro spider toxin (JSTX) isolated from Nephila clavata was shown to inhibit L-glutamate binding to rat brain synaptic membranes in a dose-dependent manner. 2,4-Dihydroxyphenylacetic acid (2,4-DHPA), a common moiety of spider toxins, also inhibited specifically L-glutamate binding at a concentration similar to that of the toxin. The binding activity inhibited by 2,4-DHPA or JSTX was recoverable on addition of ferric compound. These results suggest that 2,4-DHPA is a functional moiety in the toxin molecule and the biological action of spider toxin is explained by direct interaction with an Fe-S center which is known to play an important role for the glutamate binding.