Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying...

The calcitonin receptor-like receptor (CRLR) can function as a receptor for either calcitonin gene-related peptide (CGRP) or adrenomedullin (AM), depending upon co-expression with members of a novel family of receptor activity-modifying proteins (RAMP). RAMP1 presents the CRLR at the cell surface as a CGRP/AM receptor. RAMP2- and RAMP3-transported CRLR receptors act as AM-specific receptors. However, it is still unknown if this signalling system operates in vivo. Of particular interest is the uterus, where both peptides and their binding sites are known to be present and where both mitogenic and vasodilatory responses to AM and CGRP have been demonstrated. In this study, we examined whether CRLR and RAMP are co-expressed in the same populations of cells in human uterine tissue. Analysis by in-situ hybridization and immunocytochemistry revealed a heterogeneous and cell type-specific distribution of components of this AM/CGRP signalling system. Adrenomedullin mRNA was expressed and evenly distributed across all cell types. CRLR mRNA was predominantly found in blood vessels. RAMP1 expression was specific to myometrial myocytes and vascular smooth muscle cells in uterine arteries. RAMP2 and RAMP3 mRNA were not detectable by in-situ hybridization. The pattern of differential and cell-specific expression of CRLR and RAMP suggests the involvement of CRLR/RAMP1 in the processes of vasodilation, smooth muscle relaxation and angiogenesis in response to AM and CGRP in the human uterus, but also indicates that other receptors may be implicated.