Abstract
The calcitonin receptor (CTR) can dimerise with receptor activity-modifying proteins to form several distinct receptors. These receptors are each capable of responding to calcitonin gene-related peptide (CGRP) and/or amylin in vitro. Deconvoluting the role of each receptor for each ligand in vivo is, however, challenging. CGRP is widely expressed in the brain and is a key player in the pathophysiology of pain. Amylin, however, is predominantly expressed in the pancreas and is not widely expressed in the brain. We hypothesise that CTR-based receptors could act as receptors for CGRP, rather than amylin in many brain regions. We therefore aimed to investigate the spatial relationship between CGRP and CTR in pain relevant brain regions.
Brains were collected from adult (8-10 weeks) Sprague-Dawley rats and C57BL/6J mice, with three male and three female per species (12 animals total). Sections were selected containing the amygdala, parabrachial nucleus (PBN) and locus coeruleus (LC), and spinal trigeminal nucleus (Sp5). Fluorescent immunohistochemistry was performed using validated antibodies against CGRP and CTR. Fluorescence was visualised using confocal microscopy. The relative spatial expression of CGRP and/or CTR were analysed qualitatively.
Co-expression of CGRP and CTR was detected in the amygdala, PBN, and Sp5. Conversely, in the LC, only CTR was detected. Within each region, CGRP (where detected) was predominantly in fibres, whereas CTR was detected in fibres and cell bodies. The data were broadly consistent between rats and mice, and male and female.
The close proximity of CGRP and CTR in some locations suggests that CTR, or a CTR based receptor, could be responsible for some CGRP signalling in the brain. Conversely, in the LC, where only CTR was detected, other ligands may be involved. These data contribute to understanding CGRP receptor biology and which receptor(s) could be contributing to its modulation of pain signalling and beyond.