3-Nitropropionic acid exacerbates [3H]GABA release evoked by glucose deprivation in rat striatal slices.
3-Nitropropionic acid (3-NPA) is a metabolic poison that produces lesions of striatal intrinsic neurones such as gamma-aminobutyric acid (GABA) neurones. This study was carried out to determine whether 3-NPA would impair the ability of striatal GABAergic neurones to withstand hypoglycaemic stress. 3-NPA (500 microM) did not affect [3H]GABA release from striatal slices under normal (11 mM) glucose concentrations. When the glucose concentration was lowered to 0.3 mM, however, 3-NPA greatly potentiated the leakage of [3H]GABA from the slices. Blockage of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors with 1 microM 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) or 10 microM 2,3-dihydroxy-6-nitro-7-sulpha-moylbenzo[F]quinoxaline (NBQX), respectively, or a combination of both, had no effect. However, blockade of voltage-dependent sodium channels with tetrodotoxin totally antagonized the [3H]GABA overflow induced by the combination of 3-NPA and hypoglycaemis. Riluzole (10 to 100 microM), a neuroprotective agent that stabilizes the inactivated state of the voltage-dependent sodium channel, also dose-dependently antagonized the increase in [3H]GABA release induced by the combination of the two stresses.
Boireau
A
A
Rhône-Poulenc Rorer S.A., Centre de Recherche de Vitry-Alfortville, Département Biologie, Vitry-sur-Seine, France.
Meunier
M
M
Doble
A
A
D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007003:Hypoglycemia / Q000503:physiopathology; D007553:Isotope Labeling; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity*; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012044:Regression Analysis; D015222:Sodium Channels / Q000187:drug effects; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D014316:Tritium; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D005947:Glucose; C015392:3-nitropropionic acid