Conantokin-G: a novel peptide antagonist to the N-methyl-D-aspartic acid (NMDA) receptor.
Conantokin-G is a 17 amino acid peptide isolated from the venom of the fish-eating snail Conus geographus which produces hyperactivity when injected into the brains of adult mice. We show that this peptide is a selective N-methyl-D-aspartate (NMDA) antagonist based on its ability to block NMDA-induced elevation of cGMP in rat cerebellar slices in vitro (IC50 = 171 nM), but not kainic acid-induced elevations. This inhibition could not be overcome by increasing the NMDA concentration, indicating non-competitive inhibition. Conantokin-G displayed no affinity for binding sites for thienylcyclohexylpiperidine, various glutamate subclasses or those for several other neurotransmitters/neuromodulators. This peptide, however, enhanced [3H]glycine binding to rat forebrain membranes but not to spinal cord membranes. The activity profile of the peptide in various assays indicates that it is a novel type of non-competitive NMDA antagonist.
Mena
E E
EE
Department of Neuroscience, Pfizer Inc., Groton, CT 06340.
Gullak
M F
MF
Pagnozzi
M J
MJ
Richter
K E
KE
Rivier
J
J
Cruz
L J
LJ
Olivera
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins; D006152:Cyclic GMP / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014316:Tritium
D020916:Conotoxins; D005971:Glutamates; D010456:Peptides, Cyclic; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D016202:N-Methylaspartate; C012058:tenocyclidine; C055407:conotoxin GV; D006152:Cyclic GMP; D010622:Phencyclidine; D007608:Kainic Acid; D005998:Glycine