2572680

Inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in the neonatal rat hippocampus by 2-amino-3-phosphonopropionate.

Article date: 1989/12/1

PubMed ID: 2572680

Journal name: Journal of neurochemistry (ISSN: 0022-3042)

ABSTRACT

The effects of excitatory amino acid agonists and alpha-amino-omega-phosphonocarboxylic acid antagonists on phosphoinositide hydrolysis in hippocampal slices of the 7-day neonatal rat were examined. Significant stimulation of [3H]inositol monophosphate formation was observed with ibotenate, quisqualate, L-glutamate, L-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, L-homocysteate, and kainate. N-Methyl-D-aspartate had no effect. Of these agonists, ibotenate and quisqualate were the most potent and efficacious. Stimulations by ibotenate and quisqualate were partially inhibited by L-2-amino-4-phosphonobutyrate (10(-3) M), but this antagonist had no effect on L-glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, or kainate. At 10(-3) M, D,L-2-amino-3-phosphonopropionate completely inhibited ibotenate and quisqualate stimulations, partially inhibited L-glutamate stimulation, and had no effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-, kainate-, or carbachol-induced [3H]inositol monophosphate formation. Concentration-effect experiments showed D,L-2-amino-3-phosphonopropionate to be five times more potent as an antagonist of ibotenate-stimulated phosphoinositide hydrolysis than L-2-amino-4-phosphonobutyrate. Thus in the neonatal rat hippocampus, like in the adult rat brain, D,L-2-amino-3-phosphonopropionate is a selective and relatively potent inhibitor of excitatory amino acid-stimulated phosphoinositide hydrolysis. Because this glutamate receptor is uniquely sensitive to D,L-2-amino-3-phosphonopropionate, these studies provide further pharmacological evidence for the existence of a novel excitatory amino acid receptor subtype that is coupled to phosphoinositide hydrolysis in brain.

Author List: Schoepp D D, Johnson B G

Publication Types: Journal Article

Substances mentioned in the article: Amino Acids; Chlorides; Neurotransmitter Agents; Oxadiazoles; Phosphatidylinositols; 2-amino-3-phosphonopropionic acid; Ibotenic Acid; Aspartic Acid; Inositol; N-Methylaspartate; Quisqualic Acid; Carbachol; Lithium; Lithium Chloride; Alanine; Kainic Acid;

Mesh terms: Alanine/pharmacology; Amino Acids/pharmacology; Animals; Animals, Newborn; Aspartic Acid/pharmacology; Carbachol/pharmacology; Chlorides/pharmacology; Hippocampus/drug effects; Hydrolysis; Ibotenic Acid/pharmacology; In Vitro Techniques; Inositol/metabolism; Kainic Acid/pharmacology; Kinetics; Lithium/pharmacology; Lithium Chloride; N-Methylaspartate; Neurotransmitter Agents/pharmacology; Oxadiazoles/pharmacology; Phosphatidylinositols/metabolism; Quisqualic Acid; Rats; Rats, Inbred Strains;

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