The spider toxin, argiotoxin636, binds to a Mg2+ site on the N-methyl-D-aspartate receptor complex.
1. The mechanism of action of the arylalkylamine spider toxin, argiotoxin636, on the N-methyl-D-aspartate (NMDA) receptor was investigated by use of [3H]-dizocilpine binding to well-washed membranes obtained from rat brain. 2. Argiotoxin636 decreased [3H]-dizocilpine binding with an apparent potency of about 3 microM. The inhibition of [3H]-dizocilpine by argiotoxin636 was insensitive to the concentration of glutamate, glycine and spermidine in the assay. 3. Argiotoxin636 alone had no effect on the dissociation of [3H]-dizocilpine. However, argiotoxin636 reversed the actions of Mg2+ on the dissociation of [3H]-dizocilpine by decreasing the apparent potency of Mg2+. Argiotoxin636 also reversed the action of Ca2+ on the dissociation of [3H]-dizocilpine. 4. These results suggest that argiotoxin636 exerts a novel inhibitory effect on the NMDA receptor complex by binding to one of the Mg2+ sites located within the NMDA-operated ion channel.
Reynolds
I J
IJ
Department of Pharmacology, University of Pittsburgh, PA 15261.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D016291:Dizocilpine Maleate; D066298:In Vitro Techniques; D007210:Indoleacetic Acids; D008024:Ligands; D008274:Magnesium / Q000378:metabolism*; D010648:Phenylacetates / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*
D007210:Indoleacetic Acids; D008024:Ligands; D010648:Phenylacetates; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; C558368:argiotoxin-636; D016291:Dizocilpine Maleate; D008274:Magnesium