Abstract
Abstract: Conantokins T and G are polypeptide toxins present in snails of the genus Conus. These substances were recently reported to act as N‐methyl‐D‐aspartate (NMDA) antagonists. In the present study, we examined the possible mechanisms producing this antagonism. Conantokin‐G inhibited spermine‐ and spermidine‐stimulated [3H]MK‐801 binding to extensively washed rat forebrain membranes in a noncompetitive manner with IC50 values of ∼507 and ∼946 nM, respectively. In contrast, glutamate‐enhanced [3H]MK‐801 binding was unaffected by conantokin‐G concentrations of <20 μM. At concentrations >5 μM, conantokin‐G effected a modest, noncompetitive inhibition of glycine‐stimulated [3H]MK‐801 binding and also produced a small enhancement of basal [3H]MK‐801 binding. Conan tokin‐G reduced (IC50∼1.08 μM) the NMDA‐stimulated accumulation of cyclic GMP in cerebellar granule cell cultures to basal values, but did not affect kainate‐mediated increases in cyclic GMP. These findings indicate that conantokin‐G acts as a noncompetitive NMDA antagonist through an allosteric inhibition of polyamine responses. The neurochemical profile of this polypeptide is distinct from previously described noncompetitive NMDA antagonists.
Original language | English |
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Pages (from-to) | 1516-1521 |
Number of pages | 6 |
Journal | Journal of Neurochemistry |
Volume | 59 |
Issue number | 4 |
DOIs | |
State | Published - Oct 1992 |
Externally published | Yes |
Keywords
- Conantokin‐G
- Glycine
- MK‐801
- N‐Methyl‐D‐aspartate
- Polyamines
- Spermidine
- Spermine