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.
D000818:Animals; D001180:Arthropod Venoms / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides; D005290:Ferric Compounds / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008968:Molecular Conformation; D010648:Phenylacetates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D001180:Arthropod Venoms; D002712:Chlorides; D005290:Ferric Compounds; D005971:Glutamates; C044936:JSTX spider toxin; D010648:Phenylacetates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D013111:Spider Venoms; D018698:Glutamic Acid; C054012:2,4-dihydroxyphenylacetic acid; C024555:ferric chloride