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Titolo:
The brain metabolite kynurenic acid inhibits alpha 7 nicotinic receptor activity and increases non-alpha 7 nicotinic receptor expression: Physiopathological implications
Autore:
Hilmas, C; Pereira, EFR; Alkondon, M; Rassoulpour, A; Schwarcz, R; Albuquerque, EX;
Indirizzi:
Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 t Therapeut, Baltimore, MD 21201 USA Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USAUniv Maryland Baltimore MD USA 21201 iat Res Ctr, Baltimore, MD 21201 USA Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Inst Ciencias Biomed, Dept Farmacol Basica & Clin, BR-21944 Rio De Janeiro, Brazil Univ Fed Rio de Janeiro Rio De Janeiro Brazil BR-21944 e Janeiro, Brazil
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 19, volume: 21, anno: 2001,
pagine: 7463 - 7473
SICI:
0270-6474(20011001)21:19<7463:TBMKAI>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE RECEPTOR; ACETYLCHOLINE-RECEPTORS; HIPPOCAMPAL-NEURONS; NMDA-RECEPTORS; RAT-BRAIN; PHARMACOLOGICAL CHARACTERIZATION; CHOLINERGIC RECEPTORS; ALZHEIMERS-DISEASE; CA1 INTERNEURONS; DOPAMINE RELEASE;
Keywords:
nicotinic ACh receptors; NMDA receptors; hippocampus; kynurenic acid; electrophysiology; brain slices;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
72
Recensione:
Indirizzi per estratti:
Indirizzo: Albuquerque, EX Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, 655 W Baltimore St, Baltimore, MD 21201 USA Univ Maryland 655 W Baltimore StBaltimore MD USA 21201 SA
Citazione:
C. Hilmas et al., "The brain metabolite kynurenic acid inhibits alpha 7 nicotinic receptor activity and increases non-alpha 7 nicotinic receptor expression: Physiopathological implications", J NEUROSC, 21(19), 2001, pp. 7463-7473

Abstract

The tryptophan metabolite kynurenic acid (KYNA) has long been recognized as an NMDA receptor antagonist. Here, interactions between KYNA and the nicotinic system in the brain were investigated using the patch-clamp techniqueand HPLC. In the electrophysiological studies, agonists were delivered viaa U-shaped tube, and KYNA was applied in admixture with agonists and via the background perfusion. Exposure (greater than or equal to4 min) of cultured hippocampal neurons to KYNA (greater than or equal to 100 nm) inhibited activation of somatodendritic alpha7 nAChRs; the IC50 for KYNA was similar to7 muM. The inhibition of alpha7 nAChRs was noncompetitive with respect tothe agonist and voltage independent. The slow onset of this effect could not be accounted for by an intracellular action because KYNA (1 mm) in the pipette solution had no effect on alpha7 nAChR activity. KYNA also blocked the activity of preterminal/presynaptic alpha7 nAChFs in hippocampal neuronsin cultures and in slices. NMDA receptors were less sensitive than alpha7 nAChRs to KYNA. The IC50 values for KYNA-induced blockade of NMDA receptorsin the absence and presence of glycine (10 muM) were similar to 15 and 235muM, respectively. Prolonged (3 d) exposure of cultured hippocampal neurons to KYNA increased their nicotinic sensitivity, apparently by enhancing alpha4 beta2 nAChR expression. Furthermore, as determined by HPLC with fluorescence detection, repeated systemic treatment of rats with nicotine caused a transient reduction followed by an increase in brain KYNA levels. These results demonstrate that nAChRs are targets for KYNA and suggest a functionally significant cross talk between the nicotinic cholinergic system and thekynurenine pathway in the brain.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 07:04:33