Isolations of N-methyl-D-aspartic acid-type glutamate receptor ligands from Micronesian sponges.
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.
Sakai
Ryuichi
R
Kitasato University School of Fisheries Sciences, Sanriku-cho, Ofunato, Iwate 022-0101 Japan. r.sakai@kitasato-u.ac.jp
Matsubara
Hiroki
H
Shimamoto
Keiko
K
Jimbo
Mituru
M
Kamiya
Hisao
H
Namikoshi
Michio
M
D000818:Animals; D001921:Brain / Q000187:drug effects; D002264:Carboxylic Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008024:Ligands; D008297:Male; D051379:Mice; D008849:Micronesia; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D019029:Palau; D010880:Piperidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D013237:Stereoisomerism
D002264:Carboxylic Acids; D008024:Ligands; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C478447:cribronic acid