Glutamate receptor desensitization block potentiates the stimulated GABA release through external Ca2+-independent mechanisms from granule cells of olfactory bulb.
Glutamate stimulated release of [3H]GABA was studied, during receptor desensitization block and its modulation by voltage gated Ca2+ channels, internal Ca2+ mobilization and GABA transport inhibitors from olfactory bulb slices. Under control conditions, glutamate and agonists induced release was strongly inhibited by Mg/0 Ca2+ Krebs and Cd2+ and partially inhibited by Ni2+ and nifedipine. Cyclothiazide, which blocks desensitization of glutamate receptors, potentiated glutamate, kainate, AMPA and quisqualate induced release. This effect was less dependent of entry of external Ca2+, but was inhibited by trifluoperazine and thapsigargin, inhibitors of Ca2+-calmodulin and endoplasmatic Ca2+ ATPase respectively. Nipecotic acid and NO-711, inhibitors of the GABA transporter, were also able to reduce cyclothiazide potentiated release induced by the 4 secretagogues. Under control conditions, glutamate stimulates the release of GABA in cooperation with VDCC. However, during receptor desensitization block, glutamate stimulated GABA release is mainly modulated through mechanisms dependent on internal Ca2+ mobilization and reversal of the GABA transporter.
Jaffe
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EH
Laboratorio Neuroquimica, Centro Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela. ejaffe@cbb.ivic.ve
Figueroa
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D000818:Animals; D002118:Calcium / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D017470:Receptors, Glutamate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D011189:Potassium Chloride; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D002118:Calcium