Coupling of Inositol Phospholipid Metabolism with Excitatory Amino Acid Recognition Sites in Rat Hippocampus |
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| Authors: | F Nicoletti J L Meek M J Iadarola D M Chuang B L Roth E Costa |
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| Institution: | Laboratory of Preclinical Pharmacology, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D.C., U.S.A.;Naval Medical Research Institute, Surgical Research Branch, Bethesda, Maryland, U.S.A. |
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| Abstract: | Ibotenate, a rigid structural analogue of glutamate, markedly enhances the hydrolysis of membrane inositol phospholipids, as reflected by the stimulation of 3H]inositol monophosphate formation in rat hippocampal slices prelabeled with 3H]inositol and treated with Li+. Quisqualate, homocysteate, L-glutamate, and L-aspartate also induce a significant (albeit weaker) increase in 3H]inositol monophosphate formation, whereas N-methyl-D-aspartate, kainate, quinolinate, and N-acetylaspartylglutamate are inactive. The increase in 3H]inositol monophosphate formation elicited by the above-mentioned excitatory amino acids is potently and selectively antagonized by DL-2-amino-4-phosphonobutyric acid, a dicarboxylic amino acid receptor antagonist. These results suggest that, in the hippocampus, a class of dicarboxylic amino acid recognition sites is coupled with phospholipase C, the enzyme that catalyzes the hydrolysis of membrane inositol phospholipids. |
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| Keywords: | Ibotenate Glutamate Inositol phospholipids dl-2-Amino-4-phosphonobutyric acid Hippocampus |
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