mRNA expression of novel CGRP1 receptors and their activity-modifying proteins in hypoxic rat lung

Calcitonin gene-related peptide (CGRP) is a potent vasodilator. Our group h as reported that exogenous CGRP may prevent or reverse hypoxic pulmonary hy pertension in rats. The vasodilatory action of CGRP is mediated primarily b y CGRP1 receptors. The calcitonin receptor-like receptor (CRLR) and the orp han receptor RDC-1 have been proposed as CGRP1 receptors, and recent eviden ce suggests that CRLR can function as either a CGRP1 receptor or an adrenom edullin (ADM) receptor. Receptor activity-modifying proteins (RAMPs) determ ine the ligand specificity of CRLR: coexpression of CRLR and RAMP1 results in a CGRP1 receptor, whereas coexpression of CRLR and RAMP2 or -3 results i n an ADM receptor. We used qualitative, semiquantitative, and real-time qua ntitative RT-PCR to detect and quantitate the relative expression of these agents in the lungs of rats exposed to normoxia (n = 3) and 1 and 2 wk of c hronic hypobaric hypoxia (barometric pressure 380 mmHg, equivalent to an in spired O-2 level of 10%; n = 3/ time period). Our results show upregulation of RDC-1, RAMP1, and RAMP3 mRNAs in hypoxic rat lung and no change in CRLR and RAMP2 mRNAs. These findings support a functional role for CGRP and ADM receptors in regulating the adult pulmonary circulation.