Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.
Headache. 2010 May;50(5):834-43. doi: 10.1111/j.1526-4610.2009.01574.x. Epub 2009 Nov 17.
To examine the efficacy of L-kynurenine and a novel kynurenic acid derivative on the nitroglycerin-induced calmodulin-dependent protein kinase II alpha (CamKIIalpha) and calcitonin gene-related peptide (CGRP) expression changes in the rat caudal trigeminal nucleus.
Systemic administration of the nitric oxide donor nitroglycerin can trigger an attack in migraineurs. In the rat, nitroglycerin activates second-order neurons in the caudal trigeminal nucleus, and increases expression of the CamKIIalpha and decreases that of the CGRP there. As glutamatergic mechanisms may be crucial in trigeminal pain processing, the aim of our study was to examine the effects of L-kynurenine, a metabolic precursor of the N-methyl D-aspartate receptor antagonist kynurenic acid, on the nitroglycerin-induced changes in CamKIIalpha and CGRP immunoreactivity.
One hour before the nitroglycerin (10 mg/kg bodyweight, s.c.) injection, the animals were pretreated with L-kynurenine (300 mg/kg bodyweight, i.p.) or 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride (300 mg/kg bodyweight, i.p.), a novel kynurenic acid derivative. Four hours later, the rats were perfused transcardially and the cervical spinal cord segments were removed for immunohistochemistry. Results.- L-kynurenine and 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride pretreatment attenuated the nitroglycerin-induced changes in CamKIIalpha and CGRP immunoreactivity in the rat caudal trigeminal nucleus.
These findings suggest a mechanism by which the inhibition of the excitatory amino acid receptors by kynurenic acid and its derivatives can alter trigeminal nociception.
研究 L-犬尿氨酸和一种新型的犬尿烯酸衍生物对硝酸甘油诱导的大鼠尾状三叉神经核钙调蛋白依赖性蛋白激酶 IIα（CamKIIα）和降钙素基因相关肽（CGRP）表达变化的疗效。
系统给予一氧化氮供体硝酸甘油可引发偏头痛患者的发作。在大鼠中，硝酸甘油激活尾状三叉神经核的二级神经元，并增加那里的 CamKIIα表达，减少 CGRP 表达。由于谷氨酸能机制可能在三叉神经疼痛处理中至关重要，我们的研究目的是研究 L-犬尿氨酸（N-甲基-D-天冬氨酸受体拮抗剂犬尿烯酸的代谢前体）对硝酸甘油诱导的 CamKIIα和 CGRP 免疫反应变化的影响。
在给予硝酸甘油（10mg/kg 体重，皮下注射）前 1 小时，动物预先用 L-犬尿氨酸（300mg/kg 体重，腹腔注射）或 2-（2-N，N-二甲氨基乙基）-1H-喹啉-4-酮盐酸盐（300mg/kg 体重，腹腔注射）预处理。 4 小时后，通过心脏灌注处死大鼠，取出颈段脊髓进行免疫组织化学染色。结果.-L-犬尿氨酸和 2-（2-N，N-二甲氨基乙基）-1H-喹啉-4-酮盐酸盐预处理可减轻硝酸甘油诱导的大鼠尾状三叉神经核 CamKIIα和 CGRP 免疫反应变化。
这些发现表明，通过犬尿烯酸及其衍生物抑制兴奋性氨基酸受体可以改变三叉神经痛觉。
