Kynurenate Derivative Attenuates the Nitroglycerin‐Induced CamKIIα and CGRP Expression Changes |
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Authors: | Enik? Vámos MSc Annamária Fejes MSc Júlia Koch MD János Tajti MD PhD Ferenc Fülöp PhD DSc József Toldi PhD DSc Árpád Párdutz MD PhD László Vécsei MD PhD DSc |
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Institution: | 1. From the Department of Neurology, Albert Szent‐Gy?rgyi Clinical Centre, University of Szeged, Szeged, Hungary (E. Vámos, A. Fejes, J. Koch, J. Tajti, á. Párdutz, and L. Vécsei);2. Department of Pharmaceutical Chemistry, University of Szeged, Szeged, Hungary (F. Fül?p);3. Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary (J. Toldi). |
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Abstract: | (Headache 2010;50:834‐843) Objective.— To examine the efficacy of L‐kynurenine and a novel kynurenic acid derivative on the nitroglycerin‐induced calmodulin‐dependent protein kinase II alpha (CamKIIα) and calcitonin gene‐related peptide (CGRP) expression changes in the rat caudal trigeminal nucleus. Background.— 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 CamKIIα 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 CamKIIα and CGRP immunoreactivity. Methods.— 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 CamKIIα and CGRP immunoreactivity in the rat caudal trigeminal nucleus. Conclusions.— 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. |
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Keywords: | calmodulin‐dependent protein kinase II alpha calcitonin gene‐related peptide caudal trigeminal nucleus L‐kynurenine 2‐(2‐N N‐dimethylaminoethylamine‐1‐carbonyl)‐1H‐quinolin‐4‐one hydrochloride |
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