Both 5-HT1B and 5-HT1F receptors modulate c-fos expression within rat trigeminal nucleus caudalis.
A possible mechanism of action of antimigraine drugs such as sumatriptan is inhibition of the trigeminovascular pathway. Sumatriptan's effects might be mediated by 5-HT1B, 5-HT1D or 5-HT1F receptors. To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective 5-HT1F receptor agonist (LY 344864) on c-fos protein expression in the trigeminal nucleus caudalis. c-fos expression was induced in urethane-anaesthetized rats by intracisternal capsaicin administration. Sumatriptan and LY 344864 decreased the number of capsaicin-induced c-fos-like immunoreactive cells within trigeminal nucleus caudalis (ID50 = 0.04 and 0.6 mg kg(-1)). The effect of sumatriptan, but not of LY 344864, was prevented by pretreatment with the antagonist SDZ 21-009, which displays high affinity for rat 5-HT1B receptors. LY 344864 appears to attenuate c-fos-like immunoreactivity via 5-HT1F receptors, while sumatriptan acts via 5-HT1B receptors. The fact that activation of 5-HT1F receptors is sufficient to modulate the activity of the trigeminal system suggests that this receptor may be a target for antimigraine drugs with improved safety profile.
Mitsikostas
D D
DD
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
Sanchez del Rio
M
M
Moskowitz
M A
MA
Waeber
C
C
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000633:toxicity; D002227:Carbazoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005464:Fluorobenzenes / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D005464:Fluorobenzenes; C109453:LY 344864; D016760:Proto-Oncogene Proteins c-fos; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C038186:4-(2-hydroxy-3-tert-butylaminopropoxy)-2-methylindole; D018170:Sumatriptan; D010869:Pindolol; D002211:Capsaicin