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 has reported that exogenous CGRP may prevent or reverse hypoxic pulmonary hypertension in rats. The vasodilatory action of CGRP is mediated primarily by CGRP1 receptors. The calcitonin receptor-like receptor (CRLR) and the orphan receptor RDC-1 have been proposed as CGRP1 receptors, and recent evidence suggests that CRLR can function as either a CGRP1 receptor or an adrenomedullin (ADM) receptor. Receptor activity-modifying proteins (RAMPs) determine the ligand specificity of CRLR: coexpression of CRLR and RAMP1 results in a CGRP1 receptor, whereas coexpression of CRLR and RAMP2 or -3 results in an ADM receptor. We used qualitative, semiquantitative, and real-time quantitative 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 chronic hypobaric hypoxia (barometric pressure 380 mmHg, equivalent to an inspired 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.
Qing
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Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Svaren
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Keith
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D000818:Animals; D001483:Base Sequence / Q000235:genetics; D003199:Computer Systems; D000860:Hypoxia / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D054387:Receptors, CXCR; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C501898:Ackr3 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C545508:Ramp1 protein, rat; C545509:Ramp2 protein, rat; C545510:Ramp3 protein, rat; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D054387:Receptors, CXCR; D018015:Receptors, Calcitonin Gene-Related Peptide; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide