GABA release triggered by the activation of neuron-like non-NMDA receptors in cultured type 2 astrocytes is carrier-mediated.
Kainate (KA), quisqualate (QA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) stimulated gamma-aminobutyric acid [3H]gamma-aminobutyric acid (GABA) release from cultured cerebellar type 2 astrocytes and from their bipotential precursors. The evoked release was prevented by the antagonist 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX). AMPA and QA applied together with KA at concentrations around or above their EC50S (20-50 microM) antagonized the stimulatory effect of KA on [3H]GABA release. On the other hand, the releasing action of KA was potentiated by concentrations of QA in the low micromolar range (2-5 microM), particularly when the concentration of KA was at the borderline of effectiveness (10 microM). KA and QA did not elevate intracellular cyclic GMP levels in astrocyte cultures, although guanylate cyclase was present in both type 2 and type 1 astrocytes. The inability of KA to elevate cyclic GMP levels in astrocytes was the only major difference in the behavior of this glutamate agonist between astroglial and neuronal cultures. The GABA transport inhibitor nipecotic acid or replacement of NaCl with LiCl abolished [3H]GABA uptake and also KA- and QA-induced release of preaccumulated [3H]GABA. Therefore, [3H]GABA was released from type 2 astrocytes and their progenitors through its Na(+)-dependent transport system, operating in an outward direction when the cells were depolarized by non-NMDA receptor agonists.
Section of Neurobiology, Istituto Superiore di Sanità, Rome, Italy.
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Gallo
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Patrizio
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Levi
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D002712:Chlorides / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009557:Nipecotic Acids / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D027361:Organic Anion Transporters; D011392:Proline / Q000031:analogs & derivatives*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D012964:Sodium / Q000502:physiology*; D013268:Stimulation, Chemical; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002352:Carrier Proteins; D002712:Chlorides; D006152:Cyclic GMP; D050485:GABA Plasma Membrane Transport Proteins; D007051:Ibotenic Acid; D007608:Kainic Acid; D007736:Kynurenic Acid; D008094:Lithium; D018021:Lithium Chloride; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009557:Nipecotic Acids; D009599:Nitroprusside; D027361:Organic Anion Transporters; D011392:Proline; D011810:Quinoxalines; D016318:Quisqualic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter; D012964:Sodium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005680:gamma-Aminobutyric Acid; C030278:nipecotic acid; C010983:homoproline