Changes in the amino acid content of nerve endings (synaptosomes) induced by drugs that alter the metabolism of glutamate and gamma-aminobutyric acid.
The study was centered on the changes in the amino acid content of nerve endings (synaptosomes) induced by drugs that alter the metabolism of glutamate or gamma-aminobutyric acid (GABA), and that possess convulsant or anticonvulsant properties. The onset of seizures induced by various convulsant agents was associated with a decreased content of GABA and an increased content of glutamate in synaptosomes. The concurrent administration of pyridoxine prevented both the biochemical changes and the convulsions. The administration of gabaculine to mice resulted in large increases in the GABA content of synaptosomes that were counteracted by decreases in glutamate, glutamine, and aspartate levels such that the total content of the four amino acids remained unchanged. The administration of aminooxyacetic acid (0.91 mmol/kg) resulted initially in seizure activity, but subsequently in an anticonvulsant action. No simple relationship existed between the excitable state of the brain induced by aminooxyacetic acid and the changes in the synaptosomal levels of any of the amino acid transmitters. A hypothesis was, however, formulated that explained the convulsant-cum-anticonvulsant action of aminooxyacetic acid on the basis of compartmentation of GABA within the nerve endings.
D000596:Amino Acids / Q000378:metabolism*; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006834:Hydrazines / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D051379:Mice; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D011736:Pyridoxine / Q000031:analogs & derivatives / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000596:Amino Acids; D003509:Cyclohexanecarboxylic Acids; D005971:Glutamates; D006834:Hydrazines; C003257:pyridoxal phosphate gamma-glutamyl hydrazone; D000625:Aminooxyacetic Acid; C029424:hydrazine; C012987:gabaculine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011732:Pyridoxal Phosphate; C004675:4-deoxypyridoxine; D014635:Valproic Acid; D011736:Pyridoxine; D007538:Isoniazid