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The spider toxin, argiotoxin 636 , binds to a Mg 2+ site on the N‐methyl‐ d ‐aspartate receptor complex
Author(s) -
Reynolds Ian J.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb09796.x
Subject(s) - toxin , binding site , spider toxin , chemistry , receptor , stereochemistry , biology , biochemistry , glutamate receptor
1 The mechanism of action of the arylalkylamine spider toxin, argiotoxin 636 , on the N‐methyl‐ d ‐aspartate (NMDA) receptor was investigated by use of [ 3 H]‐dizocilpine binding to well‐washed membranes obtained from rat brain. 2 Argiotoxin 636 decreased [ 3 H]‐dizocilpine binding with an apparent potency of about 3 μ m . The inhibition of [ 3 H]‐dizocilpine by argiotoxin 636 was insensitive to the concentration of glutamate, glycine and spermidine in the assay. 3 Argiotoxin 636 alone had no effect on the dissociation of [ 3 H]‐dizocilpine. However, argiotoxin 636 reversed the actions of Mg 2+ on the dissociation of [ 3 H]‐dizocilpine by decreasing the apparent potency of Mg 2+ . Argiotoxin 636 also reversed the action of Ca 2+ on the dissociation of [ 3 H]‐dizocilpine. 4 These results suggest that argiotoxin 636 exerts a novel inhibitory effect on the NMDA receptor complex by binding to one of the Mg 2+ sites located within the NMDA‐operated ion channel.