Increased myocardial expression of RAMP1 and RAMP3 in rats with chronic heart failure.
Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) are potent vasodilators in humans and improved myocardial ischemia is observed after CGRP administration. Receptors for CGRP and ADM were already identified in heart. Receptor activity-modifying proteins (RAMPs) determine the ligand specificity of the calcitonin receptor-like receptor (CRLR); co-expression of RAMP1 and CRLR results in a CGRP receptor, whereas the association of RAMP2 or RAMP3 with CRLR gives an ADM receptor. As CGRP and ADM may play a beneficial role in heart failure, we investigated whether the CGRP and ADM receptors are upregulated in chronic heart failure. We have used semi-quantitative RT-PCR and Western-blot analysis to detect and quantify the mRNA and the protein of RAMP1 and RAMP3 in both atria and ventricles of failing hearts 6 months after aortic banding in rats. Our results showed for the first time an up-regulation of RAMP1 and RAMP3 mRNAs and proteins in this model of cardiac failure. No change was observed in mRNAs coding for CRLR, RAMP2, RDC1 (canine orphan receptor), and ADM. The present results suggested after congestive heart failure in adult rats, an up-regulation of the CGRP receptor (by an increase in RAMP1 that is associated with CRLR) in atria and ventricles and of ADM receptor (by increased RAMP3 expression that is associated with CRLR) in atria. These findings support a functional role for CGRP and ADM receptors to compensate the chronic heart failure in rats.
Cueille
Carine
C
INSERM-U349, Hôpital Lariboisière, Centre Viggo Petersen, 2 rue Ambroise Paré, 75475 Paris-Cedex 10, France.
Pidoux
Elisabeth
E
de Vernejoul
Marie-Christine
MC
Ventura-Clapier
Renée
R
Garel
Jean-Michel
JM
D053607:Adrenomedullin; D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D058286:Calcitonin Receptor-Like Protein; D002908:Chronic Disease; D004195:Disease Models, Animal; D006325:Heart Atria / Q000737:chemistry / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D054387:Receptors, CXCR; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C501898:Ackr3 protein, rat; C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; C545580:Calcrl protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; C545502:RAMP1 protein, human; C545503:RAMP2 protein, human; C545504:RAMP3 protein, human; 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; D054387:Receptors, CXCR; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide