Spider toxin and pertussis toxin differentiate post- and presynaptic glutamate receptors

A specific blocker of the postsynaptic glutamate receptors was found in the venom of the spider Nephila clavata. The toxin (JSTX) preferentially blocks quisqualate-type glutamate receptors in the crustacean neuromuscular synapse, squid giant synapse and hippocampal neurons in slice preparations. Following determination of the structure of JSTXs, a main component JSTX-3 with its analogs was chemically synthesized and used for the study of structure-activity relationships. 125I-labeled JSTX-3 and biotinylated JSTX-3 were synthesized for histochemical and biochemical studies of the glutamate receptors. The labeled JSTXs enabled visualization of the glutamate receptors in lobster muscle, rat cerebellum and hippocampus. By use of JSTX and pertussis toxin, a novel type of glutamate receptor (GluB receptor) was found in the crustacean neuromuscular synapse. While the postsynaptic glutamate receptor was blocked by JSTX, GluB receptor was insensitive to JSTX, but it was blocked by pertussis toxin, indicating involvement of inhibitory GTP-binding protein. Injection of GTP gamma S in the presynaptic axon mimicked the presynaptic glutamate potentials and caused presynaptic inhibitory action. Thus two types of biological toxins clearly separate the pre- and postsynaptic glutamate receptors.