L-kynurenine combined with probenecid and the novel synthetic kynurenic acid derivative attenuate nitroglycerin-induced nNOS in the rat caudal trigeminal nucleus

Systemic administration of the nitric oxide (NO) donor nitroglycerin (NTG) triggers a delayed attack without aura in many migraineurs, but not in healthy volunteers. In rats, 4 h after the systemic administration of NTG (10 mg/kg bw, s.c.), the neurons of the caudal trigeminal nucleus (TNC) are acti...

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Elmentve itt :
Bibliográfiai részletek
Szerzők: Vámos Enikő
Párdutz Árpád
Varga Hedvig
Bohár Zsuzsanna
Tajti János
Fülöp Ferenc
Toldi József
Vécsei László
Dokumentumtípus: Cikk
Megjelent: Pergamon Press 2009
Sorozat:NEUROPHARMACOLOGY 57 No. 4
doi:10.1016/j.neuropharm.2009.06.033

mtmt:1271229
Online Access:http://publicatio.bibl.u-szeged.hu/9962
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520 3 |a Systemic administration of the nitric oxide (NO) donor nitroglycerin (NTG) triggers a delayed attack without aura in many migraineurs, but not in healthy volunteers. In rats, 4 h after the systemic administration of NTG (10 mg/kg bw, s.c.), the neurons of the caudal trigeminal nucleus (TNC) are activated and the expression of neuronal NO synthase (nNOS) in the same area is increased suggesting a self-amplifying process in the trigeminal system, which seems to be crucial in migraine pathogenesis. Kynurenic acid (KYNA) and its analogues may exert modulatory effects in many neuropathological conditions, probably via N-methyl-D-aspartate (NMDA) antagonism. Since NMDA receptors play a crucial role in trigeminal pain processing, the aim of our experiments was to compare the effects Of L-kynurenine (L-KYN) combined with probenecid (PROB) or with 2-(2-N,N-dimethyiaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride alone, a newly synthetized KYNA derivative, on the NTG-induced nNOS expression in the rat TNC. Pretreatment with L-KYN (300 mg/kg bw, i.p.) together with PROB (200 mg/kg bw, i.p.) and KYNA derivative (300 mg/kg bw, i.p.) attenuated the NTG-induced nNOS expression in the rat TNC. Our data suggest that the stimulating effect of NTG, and thus of NO, on the expression of nNOS might be modulated by increasing the KYNA level in the brain, probably through the NMDA receptors. These data could help promote a better understanding of the pathogenesis of headaches and the action of antimigraine drugs. (C) 2009 Elsevier Ltd. All rights reserved. 
700 0 1 |a Párdutz Árpád  |e aut 
700 0 1 |a Varga Hedvig  |e aut 
700 0 1 |a Bohár Zsuzsanna  |e aut 
700 0 1 |a Tajti János  |e aut 
700 0 1 |a Fülöp Ferenc  |e aut 
700 0 1 |a Toldi József  |e aut 
700 0 1 |a Vécsei László  |e aut 
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