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Titolo:
Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor-mediated stimulation of glutamate and GABA release in the rat striatum in vivo: A dual-label microdialysis study
Autore:
Patel, DR; Young, AMJ; Croucher, MJ;
Indirizzi:
Charing Cross Hosp, Imperial Coll Sch Med, Dept Neuroinflammat, London W6 8RF, England Charing Cross Hosp London England W6 8RF flammat, London W6 8RF, England Univ Leicester, Dept Psychol, Behav Neurosci Grp, Leicester LE1 7RH, Leics, England Univ Leicester Leicester Leics England LE1 7RH er LE1 7RH, Leics, England
Titolo Testata:
NEUROSCIENCE
fascicolo: 1, volume: 102, anno: 2001,
pagine: 101 - 111
SICI:
0306-4522(2001)102:1<101:PAPR>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
METHYL-D-ASPARTATE; EXCITATORY AMINO-ACIDS; GAMMA-AMINOBUTYRIC-ACID; CENTRAL-NERVOUS-SYSTEM; DOPAMINE RELEASE; AMPA RECEPTORS; ACETYLCHOLINE-RELEASE; NORADRENALINE RELEASE; KAINATE RECEPTORS; BASAL GANGLIA;
Keywords:
presynaptic AMPA receptors; neurotransmitter release; microdialysis; glutamate; GABA; striatum;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
82
Recensione:
Indirizzi per estratti:
Indirizzo: Croucher, MJ Charing Cross Hosp, Imperial Coll Sch Med, Dept Neuroinflammat, Fulham Palace Rd, London W6 8RF, England Charing Cross Hosp Fulham Palace Rd London England W6 8RF nd
Citazione:
D.R. Patel et al., "Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor-mediated stimulation of glutamate and GABA release in the rat striatum in vivo: A dual-label microdialysis study", NEUROSCIENC, 102(1), 2001, pp. 101-111

Abstract

The existence of presynaptic alpha -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate autoreceptors on glutamate nerve terminals in vitro has recently been demonstrated using synaptosomal and brain slice preparations. In the present study we have used a modification of a rapid dual-label intracerebral microdialysis method, previously developed by Youngand co-workers(80,81) for the study of presynaptic mechanisms of neurotransmitter release, to investigate whether presynaptic AMPA receptors also play a role in the control of striatal glutamate release in vivo. For comparative purposes, the action of locally applied AMPA on striatal GABA release in vivo was also monitored. Local application of AMPA (0.01-100 muM), by reverse dialysis, into the striatum resulted in concentration-dependent increases in the Ca2+-dependent efflux of both [H-3]L-glutamate and [C-14]GABA. Maximum responses reached 142.0 +/- 6.5% and 166.8 +/- 7.7% of basal efflux for [H-3]L-glutamate and [C-14]GABA, respectively. No marked behavioural changes were observed at any dose of the agonist. Unexpectedly, the AMPA-evoked responses were not potentiated by the AMPA receptor desensitization inhibitors cyclothiazide (10-100 muM) or aniracetam (1 mM). Consistent with this finding, AMPA-stimulated [H-3]L-glutamate and [C-14]GABA efflux were significantly attenuated by co-perfusion with the selective, competitive AMPA receptor antagonist 6-nitro-7-sulphamoylbenzo(F)quinoxaline-2,3-dione (100 muM) but not 1-(aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepine (100 muM), a non-competitive AMPA receptor antagonist known to interact with the cyclothiazide site to control AMPA receptor function. The broad spectrum ionotropic glutamate receptor antagonist, kynurenic acid (100-1000 muM) also markedly inhibited the AMPA-evoked responses in the striatum in vivo. None of the antagonists, when given alone, influenced basal efflux of [H-3]L-glutamate suggesting a lack of tonic regulatory control of glutamate release via presynaptic AMPA-type autoreceptors in the rat striatum. These results demonstrate the presence of presynaptic AMPA receptors, of anovel cyclothiazide- and aniracetam-insensitive subtype, on presynaptic nerve terminals in the rat striatum in vivo, acting to enhance glutamate and GABA release. Our data support the concept of AMPA receptor heterogeneity in vivo, a finding which may facilitate the development of novel, more selective drugs for the treatment of a range of neurological disorders associated with abnormal cerebral glutamate release. The pharmacological profile of these novel presynaptic receptors is currently under investigation. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 08:58:11