Lesions of putative glutamatergic pathways potentiate the increase of inositol phospholipid hydrolysis elicited by excitatory amino acids.
The stimulation of inositol phospholipid (PI) hydrolysis by excitatory amino acids was measured in the rat hippocampus or striatum after 3 different chemical or surgical lesions of putative glutamatergic pathways. Intrahippocampal infusions of kainate preferentially destroyed neurons in the CA3-4 areas, denervating the CA1 area of the ipsilateral and contralateral hippocampus. Infusions of colchicine selectively destroyed granule cells of fascia dentata, denervating the CA3 area of the ipsilateral hippocampus. Ablation of the frontal cortex selectively reduced the glutamatergic afferents to the striatum. These 3 lesions potentiated the ibotenate, glutamate and quisqualate stimulation of PI hydrolysis, while N-methyl-D-aspartate remained ineffective. This stimulation was inhibited by 2-amino-4-phosphonobutyric acid but not by phencyclidine. These lesions also increased the stimulation of PI hydrolysis elicited by norepinephrine, but failed to enhance the stimulation by carbamylcholine. These results support the hypothesis that signal transduction in a subclass of excitatory amino acid receptors present in rat brain may undergo plastic modifications following denervation.
D000596:Amino Acids / Q000494:pharmacology*; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006868:Hydrolysis; D007051:Ibotenic Acid / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000502:physiology
D000596:Amino Acids; D000613:Aminobutyrates; D005971:Glutamates; D010069:Oxadiazoles; D010716:Phosphatidylinositols; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D007051:Ibotenic Acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; C012729:2-amino-4-phosphonobutyric acid; D007608:Kainic Acid; D003078:Colchicine