title: l-kynurenine combined with probenecid and the novel synthetic kynurenic acid derivative attenuate nitroglycerin-induced nNOS in the rat caudal trigeminal nucleus.
abstract: 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-dimethylaminoethylamine-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.
authors: Department of Neurology, University of Szeged, Szeged, Hungary.
authors: Eniko
authors: E
authors: Vámos
authors: Arpád
authors: A
authors: Párdutz
authors: Hedvig
authors: H
authors: Varga
authors: Zsuzsanna
authors: Z
authors: Bohár
authors: János
authors: J
authors: Tajti
authors: Ferenc
authors: F
authors: Fülöp
authors: József
authors: J
authors: Toldi
authors: László
authors: L
authors: Vécsei
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002574:Cervical Vertebrae; D004357:Drug Synergism; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D007737:Kynurenine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology; D011339:Probenecid / Q000008:administration & dosage / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors; D014278:Trigeminal Nuclei / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: C544943:2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one; D002491:Central Nervous System Agents; D020030:Nitric Oxide Donors; D015363:Quinolones; D007737:Kynurenine; D052248:Nitric Oxide Synthase Type I; D005996:Nitroglycerin; D007736:Kynurenic Acid; D011339:Probenecid