Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

Abstract

"Differential distribution of calcitonin gene-related peptide (CGRP) and CGRP receptor components (CLR and RAMP1) in the human trigeminal ganglion."Neuroscience, 2010, Jun 2 http://dx.doi.org/10.1016/j.neuroscience.2010.05.016Access to the published version may require journal subscription.Published with permission from: Elsevier Antibodies against purified CLR and RAMP1 proteins were produced and characterized for this study. Trigeminal ganglia were obtained at autopsy from adult subjects and sections from rat trigeminal ganglia were used to compare the immunostaining pattern. The number of cells expressing CGRP, CLR and RAMP1, respectively, were counted. In addition, the glial cells of trigeminal ganglion, particularly the satellite glial cell, were studied to understand a possible relation.We observed immunoreactivity for CGRP, CLR and RAMP1, in the human trigeminal ganglion: 49% of the neurons expressed CGRP, 37% CLR and 36% RAMP1. Co-localization of CGRP and the receptor components was rarely found. There were no CGRP immunoreactions in the glial cells; however some of the glial cells displayed CLR and RAMP1 immunoreactivity. Similar results were observed in rat trigeminal ganglia.We report that human and rat trigeminal neurons store CGRP, CLR and RAMP1, however, CGRP and CLR/RAMP1 do not co-localize regularly but are found in separate neurons. Glial cells also contain the CGRP receptor components but not CGRP. Our results indicate, for the first time, the possibility of CGRP signaling in the human trigeminal ganglion involving both neurons and satellite glial cells. This suggests a possible site of action for the novel CGRP receptor antagonists in migraine therapy.

Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

“…As in our previous paper on the trigeminal ganglion [7]; this procedure did not differ in immunoreactivity for CGRP, CLR and RAMP1 as compared to fixation directly of fresh brainstems (data not shown).…”

“…We have previously reported in detail the distribution of CGRP and its receptor components in the human trigeminal ganglion [7]. Small to medium sized neurons of the trigeminal ganglion store CGRP and have further connections with STN in the brainstem, and in related extensions down to the C 1-2 level via un-myelinated C-fibers [18].…”

“…Preabsorption controls with blocking peptides (details on these have been described before in [7]) were performed with all CLR and RAMP1 primary antibodies. Concentrations of the antibodies were the same as described in Table 1, peptide concentrations were 100:1.…”

“…In the central nervous system (CNS), CGRP is expressed in several regions such as the striatum, amygdalae, hypothalamus, colliculi, brainstem, cerebellum and the trigeminal complex [3-7]. Moreover, CGRP is found in primary spinal afferent C- and Aδ-fibers, which project to the brainstem.…”

“…We have investigated in detail the distribution and relationship of CGRP and its receptor components within human and rat spinal trigeminal nucleus (STN) in the brainstem and in the spinal cord at C1-level, using a set of newly characterized antibodies for immunohistochemistry [7]. Our main findings in the present work were that CGRP and the receptor components appear in different structures/regions of STN, and in lamina I and II at C1-level, but do not co-localize.…”