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

ConusVenoms: A Rich Source of Novel Ion Channel-Targeted Peptides

“…It was subsequently shown that the peptide inhibited NMDA-mediated currents in mouse brain mRNA-injected oocytes (62) and also blocked the NMDA-mediated increase in intracellular free Ca 2ϩ using cerebellar granule cells in culture (61). These experiments also suggested that conantokin-G acts as a competitive antagonist.…”

Novel Conantokins from Conus parius Venom Are Specific Antagonists of N-Methyl-D-aspartate Receptors

“…2 Conantokins were first identified by their ability to cause sleep in young mice and hyperactivity in older mice when injected intracranially (1,2). Subsequently, they were characterized as antagonists of the N-methyl-D-aspartate (NMDA) receptor class of ionotropic glutamate receptors (3)(4)(5). The first conantokin peptide purified from the venom of Conus geographus, conantokin-G (con-G), was reported over 20 years ago (1).…”

Developmental Biology of Neoplastic Growth

“…3g), was the first member of the family discovered and was isolated on the basis of its unusual bioactivity in mice: it produced a sleep-like state (McIntosh et al 1984). This "sleeper peptide" was proposed initially to target NMDA receptors based on indirect biochemical assays ) and later confirmed using physiological recordings from NMDA receptor channels (Hammerland et al 1992). Con-T was isolated from Conus tulipa based on similar behavioral effects ("sleep" induction) in mice and found to have structural similarities to con-G ); namely the initial glycine-glutamate-γ-carboxyglutamate-γ-carboxyglutamate resi-dues were conserved in the two peptides.…”

“…Con-G, the most extensively characterized conantokin, has appeared to have both competitive and noncompetitive antagonist activity in different assays for NMDA receptor function (Prorok and Castellino 2007). Competitive antagonism occurs at the glutamate binding site on the NR2 subunit (Hammerland et al 1992;Wittekindt et al 2001), with an IC 50 of ~0.5-1 μM for inhibition of NMDA-evoked currents in cultured mouse cortical neurons or for inhibition of synaptic NMDA-EPSCs in CA1 pyramidal neurons in rat hippocampal slice preparations Barton et al 2004). The molecular binding site of con-G could be heterotopic, because the inhibitory activity is enhanced by polyamines such as spermine , which binds to an extracellular allosteric modulatory site.…”

“…Conantokins are peptide antagonists selective for NMDA receptors Mena et al 1990;Hammerland et al 1992;Prorok and Castellino 2007). Con-G, the most extensively characterized conantokin, has appeared to have both competitive and noncompetitive antagonist activity in different assays for NMDA receptor function (Prorok and Castellino 2007).…”