Cox-2 inhibitor attenuates NO-induced nNOS in rat caudal trigeminal nucleus.
OBJECTIVE
The aim of the present study was to determine which isoform of the cyclooxygenase (COX) enzyme plays a role in the neuronal nitric oxide synthase (nNOS) activation caused by nitroglycerin (NTG), in the most caudal part of the trigeminal caudal nucleus (TNC) of the rat.


BACKGROUND
Nitric oxide donor, NTG, can trigger migraine attack in migraineurs, but not in healthy persons. In rats, subcutaneous administration of NTG (10 mg/kg) increases significantly the number of nNOS-immunoreactive neurons in the TNC after 4 hours, which could be attenuated by acetyl-salicylate (Aspirin), a nonselective COX-inhibitor.


METHODS
SPRD rats were divided into 3 groups: (1) control group (no drug administration), (2) NS398 (selective COX-2 inhibitor) administration (1, 3, or 5 mg/kg), and (3) SC560 (selective COX-1 inhibitor) administration (1, 5, or 10 mg/kg). Thirty minutes after drug administration, the animals received NTG (10 mg/kg) or placebo injection. Four hours later the animals were transcardially perfused and the cervical part of the TNC was removed for immunohistochemistry. Results.-The selective COX-2 inhibitor NS398 in contrast to the selective COX-1 inhibitor SC560 attenuates the NTG-induced nNOS expression dose-dependently.


CONCLUSIONS
These findings suggest that metabolites deriving from COX-2 (but not COX-1) may be the most important factors in the NTG-induced nNOS expression. These data could help to better understand the pathogenesis of headaches and the action of antimigraine drugs.
Varga
Hedvig
H
Neurology Research Group of the Hungarian Academy of Sciences and the University of Szeged, Szeged, Hungary.
Pardutz
Arpad
A
Vamos
Eniko
E
Plangar
Imola
I
Egyud
Eszter
E
Tajti
Janos
J
Bari
Ferenc
F
Vecsei
Laszlo
L
D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000201:enzymology*
D052246:Cyclooxygenase 2 Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D005996:Nitroglycerin