Conantokin-G selectively inhibits N-methyl-D-aspartate-induced currents in Xenopus oocytes injected with mouse brain mRNA.

The conantokins are a family of peptides isolated from the venom of predatory marine snails of the genus Conus. Here we demonstrate that one of these peptides, conantokin-G, specifically inhibits the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors that are expressed in mouse brain mRNA-injected Xenopus oocytes. Increasing the concentration of conantokin-G causes the NMDA dose-response curve to shift to progressively higher concentrations. We therefore conclude that conantokin-G interacts with the glutamate binding site of the receptor. In contrast, the peptide does not compete with glycine, and this indicates that conantokin-G does not act at the binding site of this co-agonist of the NMDA receptor. Furthermore, the inhibitory effects of conantokin-G appear to be insensitive to membrane potential.