Release of [(3)H]-L-glutamate by stimulation of nicotinic acetylcholine receptors in rat cerebellar slices.
This is a neurochemical study which shows that nicotine acting through alpha7-containing nicotinic acetylcholine receptors promotes the release of [(3)H]-glutamate from rat cerebellar slices. Release evoked by half maximal concentration of nicotine (100 microM) was blocked by alpha-bungarotoxin and in a calcium-free medium, suggesting an effect mediated by an alpha7 receptor. Dihydro-beta-erythroidine and mecamylamine were effective only at very high concentrations, excluding the participation of heteromeric receptors. The effect of nicotine was partially blocked by inhibitors of glutamatergic receptors DL-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, indicating a glutamate-induced glutamate release. Nicotine-evoked response was dependent on activation of tetrodotoxin sensitive sodium channels. Therefore, here we show that glutamate released by stimulation of alpha7-containing nicotinic receptors, located preterminal and/or postsynaptically, evokes a further glutamate release in adult rat cerebellar slices.
Laboratório de Cronofarmacologia, Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, Travessa 14, 05508-900 São Paulo, Brazil.
L A C
LA
Reno
W
W
Zago
R P
RP
Markus
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014316:Tritium; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D018691:Excitatory Amino Acid Antagonists; D018733:Nicotinic Antagonists; D017470:Receptors, Glutamate; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D064569:alpha7 Nicotinic Acetylcholine Receptor; D014316:Tritium; D018698:Glutamic Acid; D011189:Potassium Chloride; D009538:Nicotine