丙磺舒
巴比妥酸
化学
犬尿氨酸
药理学
细胞外
NMDA受体
兴奋性突触后电位
神经毒性
内分泌学
内科学
生物化学
受体
毒性
氨基酸
生物
医学
色氨酸
有机化学
作者
Julie Miller,Usha MacGarvey,M. Flint Beal
标识
DOI:10.1016/0304-3940(92)90186-b
摘要
Kynurenic acid (KYA) is the only known endogenous excitatory amino acid antagonist in mammalian brain. In the present study we examined the effects of precursor loading with kynurenine (KYN) and blockade of organic acid transport with probenecid, either alone or in combination, on extracellular striatal KYA concentrations in unanesthetized rats. Baseline KYA concentrations were 1.61±0.29 pmol/ml. Following administration of KYN 150 mg/kg with increasing doses of probenecid a maximal increase in KYA to 946±210 pmol/ml was seen with probenecid 200 mg/kg. Probenecid 200 mg/kg alone increased KYA levels to 16.0±5.2 pmol/ml. The combination of probenecid 200 mg/kg with KYN 450 mg/kg produced a maximal increase of KYA to 2085±391 pmol/ml, a 1300-fold increase indicating marked potentiation. These results show that pharmacologic manipulation can markedly increase extracellular fluid concentrations of KYA into a range which may be useful in attempts to block NMDA receptor-mediated neurotoxicity.
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