Aspartate aminotransferase for synthesis of transmitter glutamate in the medulla oblongata: effect of aminooxyacetic acid and 2-oxoglutarate.
The effects of aminooxyacetic acid (AOAA), a transaminase inhibitor, and 2-oxoglutarate, a precursor to glutamate by the activity of aspartate aminotransferase (AAT), on slices of rat medulla oblongata, cerebellum, cerebral cortex, and hippocampus were studied. The slices were superfused and electrically stimulated. There was a Ca2+-dependent stimulus-evoked release of endogenous glutamate, gamma-aminobutyric acid (GABA), and beta-alanine in all regions examined. AOAA (10(-4) and 10(-3) M) decreased the release of glutamate in the medulla oblongata and cerebellum but not in the hippocampus. L-Canaline, a specific inhibitor of ornithine aminotransferase, did not affect the glutamate release in the medulla. 2-Oxoglutarate (10(-3) M) increased the release of glutamate in the medulla oblongata and cerebellum but not in the cerebral cortex and hippocampus. Treatment with AOAA (10(-4) M) almost abolished the activities of AAT in all regions studied. AOAA (10(-4) and 10(-3) M) increased the stimulus-evoked release of GABA in the cerebellum, cerebral cortex, and hippocampus, whereas the stimulus-evoked release of beta-alanine was decreased by this agent in all regions studied. These results suggest the participation of AAT in the synthesis of the transmitter glutamate in the medulla oblongata and cerebellum of the rat.
Kihara
M
M
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Kubo
T
T
D000085:Acetates / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D004558:Electric Stimulation; D005971:Glutamates / Q000096:biosynthesis* / Q000378:metabolism; D018698:Glutamic Acid; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D015091:beta-Alanine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000085:Acetates; D000596:Amino Acids; D005971:Glutamates; D007656:Ketoglutaric Acids; D018377:Neurotransmitter Agents; D015091:beta-Alanine; D000625:Aminooxyacetic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001219:Aspartate Aminotransferases