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.
Department of Biology, University of Utah, Salt Lake City 84112.
L G
LG
Hammerland
B M
BM
Olivera
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D
Yoshikami
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry; D020916:Conotoxins; D004594:Electrophysiology; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D008978:Mollusk Venoms / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012333:RNA, Messenger / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014981:Xenopus
D020916:Conotoxins; D005971:Glutamates; D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C055407:conotoxin GV; D005998:Glycine