title: Selective inhibition of cyclooxygenase-2 attenuates nitroglycerin-induced calmodulin-dependent protein kinase II alpha in rat trigeminal nucleus caudalis.
abstract: The nitric oxide donor, nitroglycerin (NTG) can trigger a migraine attack, after a delay of several hours in migraineurs, but not in healthy people. This long delay does not favor a pure vasodilatatory action. In rats, subcutaneous administration of NTG (10mg/kg) significantly and selectively increases the number of calmodulin-dependent protein kinase II alpha (CamKIIalpha)-immunoreactive neurons in the trigeminal caudal nucleus (TNC) after 4h. The aim of our study was to determine if any isoforms of the cyclooxygenase (COX) enzyme might have a role in the NTG-induced increase of CamKIIalpha expression. In our experiments, we demonstrated that pretreatment with NS398, the selective COX-2 inhibitor attenuated the NTG-induced CamKIIalpha expression in the TNC at doses of 3 and 5mg/kg. In contrast, SC560, a selective COX-1 inhibitor failed to modulate this phenomenon in any of the dosages used (1, 5 and 10mg/kg). These findings suggest that COX-2, but not COX-1 derived metabolites are important factors in the NTG-induced CamKIIalpha expression. Thus this isoform may play a significant role in the induction of migraine. These data could help in the better understanding of the pathogenesis of headaches and the action of antimigraine drugs.
authors.affiliation: Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
authors.forename: Hedvig
authors.initials: H
authors.lastname: Varga
authors.forename: Arpad
authors.initials: A
authors.lastname: Pardutz
authors.forename: Eniko
authors.initials: E
authors.lastname: Vamos
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bohar
authors.forename: Ferenc
authors.initials: F
authors.lastname: Bago
authors.forename: Janos
authors.initials: J
authors.lastname: Tajti
authors.forename: Ferenc
authors.initials: F
authors.lastname: Bari
authors.forename: Laszlo
authors.initials: L
authors.lastname: Vecsei
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000187:drug effects* / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000187:drug effects* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D009578:Nitrobenzenes / Q000494:pharmacology; D005996:Nitroglycerin / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; D014665:Vasodilator Agents; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005996:Nitroglycerin