1. Isolations of N-methyl-D-aspartic acid-type glutamate receptor ligands from Micronesian sponges.
- Author
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Sakai R, Matsubara H, Shimamoto K, Jimbo M, Kamiya H, and Namikoshi M
- Subjects
- Animals, Brain drug effects, Carboxylic Acids chemistry, Carboxylic Acids pharmacology, Dose-Response Relationship, Drug, Inhibitory Concentration 50, Ligands, Male, Mice, Micronesia, Molecular Structure, Nuclear Magnetic Resonance, Biomolecular, Palau, Piperidines chemistry, Piperidines pharmacology, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate agonists, Stereoisomerism, Carboxylic Acids isolation & purification, Piperidines isolation & purification, Porifera chemistry, Receptors, N-Methyl-D-Aspartate metabolism
- Abstract
The bioassay-guided fractionation of the water-soluble extract of the marine sponge Cribrochalina olemda collected in Palau resulted in the isolation of a new amino acid cribronic acid (1): (2S,4R,5R)-5-hydroxy-4-sulfooxypiperidine-2-carboxylic acid. However, aqueous extracts of Stylotella aurantium and Axinella carteri collected in Yap State, Micronesia, afforded a known N-methyl-d-aspartic acid (NMDA)-type glutamate receptor agonist, (2S,4S)-4-sulfooxypiperidine-2-carboxylic acid (2), as a common active principle. Both 1 and 2 induced convulsive behaviors in mice upon intracerebroventricular (icv) injection with ED(50) values of 29 +/- 3.0 and 20 +/- 2.8 pmol/mouse, respectively. Radioligand binding assay using rat cerebrocortical membrane demonstrated that 1 and 2 inhibit the binding of the labeled NMDA receptor ligand [(3)H]CGP39653 at IC(50) values of 83 +/- 15 and 214 +/- 20 nM, respectively. However, 1 and 2 did not displace [(3)H]kainic acid or [(3)H]AMPA. These data indicated that 1 is a selective NMDA-type glutamate receptor ligand with potent convulsant activity in mice.
- Published
- 2003
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