mRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene–related peptide in the rat trigeminovascular system

Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT1 receptor that mediate the antimigraine effect have still to be identified. This study investigated the mRNA expression of these receptors and the role of 5-HT1 receptor subtypes in controlling the release of calcitonin gene–related peptide (CGRP) in rat dura mater, trigeminal ganglion (TG), and trigeminal nucleus caudalis (TNC). The mRNA for each receptor subtype was quantified by quantitative real-time polymerase chain reaction. A high potassium concentration was used to release CGRP from dura mater, isolated TG, and TNC in vitro. The immunoreactive CGRP (iCGRP) release was measured by enzyme-linked immunoassay. The mRNA transcripts of the 3 5-HT1 receptor subtypes were detected in the trigeminovascular system. Sumatriptan inhibited iCGRP release by 31% in dura mater, 44% in TG, and 56% in TNC. This effect was reversed by a 5-HT1B/1D antagonist (GR127395). The 5-HT1F agonist (LY-344864) was effective in the dura mater (26% iCGRP inhibition), and the 5-HT1D agonist (PNU-142633) had a significant effect in the TNC (48%), whereas the 5-HT1B agonist (CP-94253) was unable to reduce the iCGRP release in all tissues studied. We found that sumatriptan reduced the iCGRP release via activation of 5-HT1D and 5-HT1F receptor subtypes. The 5-HT1F receptor agonist was effective only in peripheral terminals in dura mater, whereas the 5-HT1D agonist had a preferential effect on central terminals in the TNC.