Glutamic acid and gamma-aminobutyric acid modulate each other's release through heterocarriers sited on the axon terminals of rat brain.
The effects of gamma-aminobutyric acid (GABA) on the spontaneous release of endogenous glutamic acid (Glu) or aspartic acid (Asp) and the effects of Glu on the release of endogenous GABA or [3H]GABA were studied in superfused rat cerebral cortex synaptosomes. GABA increased the outflow of Glu (EC50 17.2 microM) and Asp (EC50 18.4 microM). GABA was not antagonized by bicuculline or picrotoxin. Neither muscimol nor (-)-baclofen mimicked GABA. The effects of GABA were prevented by GABA uptake inhibitors and were Na+ dependent. Glu enhanced the release of [3H]GABA (EC50 11.5 microM) from cortical synaptosomes. Glu was not mimicked by the glutamate receptor agonists N-methyl-D-aspartic, kainic, or quisqualic acid. The Glu effect was decreased by the Glu uptake inhibitor D-threo-hydroxyaspartic acid (THA) and it was Na+ sensitive. Similarly to Glu, D-Asp increased [3H]GABA release (EC50 9.9 microM), an effect blocked by THA. Glu also increased the release of endogenous GABA from cortex synaptosomes. In this case the effect was in part blocked by the (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, whereas the 6-cyano-7-nitroquinoxaline-2,3-dione-insensitive portion of the effect was prevented by THA. GABA increased the [3H]D-Asp outflow (EC50 13.7 microM) from hippocampal synaptosomes in a muscimol-, (-)-baclofen-, bicuculline-, and picrotoxin-insensitive manner. The GABA effect was abolished by blocking GABA uptake and was Na+ dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Bonanno
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Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Pittaluga
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Fedele
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Fontana
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Raiteri
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D027322:Amino Acid Transport System X-AG; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects / Q000502:physiology*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009411:Nerve Endings / Q000378:metabolism; D027361:Organic Anion Transporters; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D005971:Glutamates; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid