Kynurenate derivative attenuates the nitroglycerin-induced CamKIIα and CGRP expression changes.
OBJECTIVE
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.


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 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.


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 CamKIIalpha 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.
Vámos
Eniko
E
Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.
Fejes
Annamária
A
Koch
Júlia
J
Tajti
János
J
Fülöp
Ferenc
F
Toldi
József
J
Párdutz
Arpád
A
Vécsei
László
L
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007736:Kynurenic Acid / Q000031:analogs & derivatives*; D007737:Kynurenine / Q000494:pharmacology*; D008297:Male; D005996:Nitroglycerin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D007527:Isoenzymes; D007737:Kynurenine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005996:Nitroglycerin; D007736:Kynurenic Acid; D015740:Calcitonin Gene-Related Peptide