5-HT 1B and 5-HT 1D receptors in the human trigeminal ganglion: co-localization with calcitonin gene-related peptide, substance P and nitric oxide synthase

Abstract

5-Hydroxytryptamine (5-HT) is implicated in migraine and agonist directed aganist 5-HT 1B and 5-HT 1D receptors are commonly used as effective therapies. The antimigraine mechanisms involve the inhibition of intracranial sensory neuropeptide release. In order to determine which 5-HT 1 receptor subtypes are involved we have by immunocytochemistry examined the distribution of 5-HT 1B and 5-HT 1D receptors in the human trigeminal ganglia, and addressed which of them colocalize with calcitonin gene-related peptide (CGRP), substance P (SP) or nitric oxide synthase (NOS). We detected that 5-HT 1D receptor immunoreactivity (i.r.) was predominantly expressed in medium-sized cells (86% of positive cells, 30–60 μm). About 9% of the 5-HT 1D receptor i.r. cells were large in size (>60 μm) and 5% were small in size (<30 μm). In a similar pattern, 5-HT 1B receptor i.r. was mainly expressed in medium-sized cells (81% in 30–60 μm, 15% in >60 μm and 4% in <30 μm). Double immunostaining was used to determine whether the 5-HT 1B or 5-HT 1D receptor immunoreactive cells co-localized with either CGRP, SP or NOS. Thus, 89% of the CGRP i.r. cells expressed 5-HT 1D receptor i.r. and 65% of the CGRP positive cells were 5-HT 1B receptor positive. Most of the 5-HT 1D (95%) and the 5-HT 1B (94%) receptor i.r. cells showed SP immunostaining and 83% of 5-HT 1D receptor and 86% of 5-HT 1B receptor i.r. cells contained NOS. In conclusion, both 5-HT 1B and 5-HT 1D receptors are expressed in the human trigeminal ganglion and they are mainly localized in medium-sized cells and they seem to colocalize with CGRP, SP and NOS.