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-HT ₁ 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-HT ₁ 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-HT ₁ 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-HT _1B/1D antagonist (GR127395). The 5-HT _1F agonist (LY-344864) was effective in the dura mater (26% iCGRP inhibition), and the 5-HT _1D agonist (PNU-142633) had a significant effect in the TNC (48%), whereas the 5-HT _1B 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-HT _1D and 5-HT _1F receptor subtypes. The 5-HT _1F receptor agonist was effective only in peripheral terminals in dura mater, whereas the 5-HT _1D agonist had a preferential effect on central terminals in the TNC.