Kynurenine administered together with probenecid markedly inhibits pentylenetetrazol-induced seizures. An electrophysiological and behavioural study

The kynurenine pathway converts tryptophan into various compounds, including L-kynurenine, which in turn can be converted to the excitatory amino acid receptor antagonist kynurenic acid, which may therefore serve as a protective agent in such neurological disorders as epileptic seizures. Kynurenic a...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Németh H.
Robotka Hermina
Kis Zsolt
Rózsa Éva
Janáky Tamás
Somlai Csaba
Marosi Máté Gábor
Farkas Tamás
Toldi József
Vécsei László
Dokumentumtípus: Cikk
Megjelent: Pergamon Press 2004
Sorozat:NEUROPHARMACOLOGY 47 No. 6
doi:10.1016/j.neuropharm.2004.06.007

mtmt:1030160
Online Access:http://publicatio.bibl.u-szeged.hu/10117
Leíró adatok
Tartalmi kivonat:The kynurenine pathway converts tryptophan into various compounds, including L-kynurenine, which in turn can be converted to the excitatory amino acid receptor antagonist kynurenic acid, which may therefore serve as a protective agent in such neurological disorders as epileptic seizures. Kynurenic acid, however, has a very limited ability to cross the blood-brain barrier, whereas kynurenine passes the barrier easily. In this study, we tested the hypothesis that kynurenine administered systemically together with probenecid, which inhibits kynurenic acid excretion from the cerebrospinal fluid, results in an increased level of kynurenic acid in the brain that is sufficiently high to provide protection against the development of pentylentetrazol-induced epileptic seizures. CA3 stimulation-evoked population spike activity was recorded from the pyramidal layer of area CA1 of the rat hippocampus, and in another series of behavioural experiments, water maze and open-field studies were carried out to test the presumed protective effect of kynurenine + probenecid pre-treatment against pentylenetetrazol-induced seizures. This study has furnished the first electrophysiological proof that systemic kynurenine (300 mg/kg, i.p.) and probenecid (200 mg/kg, i.p.) administration protects against pentylenetetrazol-induced (60 mg/kg, i.p.) epileptic seizures. (C) 2004 Elsevier Ltd. All rights reserved.
Terjedelem/Fizikai jellemzők:916-925
ISSN:0028-3908