title: Identification of potential pharmacological targets by analysis of the comprehensive G protein-coupled receptor repertoire in the four cardiac chambers.
abstract: Cardiac function is regulated by many hormones and neurotransmitters that exert their physiological effects through the activation of G protein-coupled receptors (GPCRs). Identification of new GPCRs that might display a specific pattern of expression within the heart and differentially regulate specific cardiac functions represents an important issue for the development of new drugs. Indeed, highly targeted receptors represent only a small percentage of known GPCRs. Here, we quantified the expression of 395 endoGPCRs (all GPCRs excluding taste and odorant receptors) in male mouse right and left atria and ventricles by using high-throughput real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and focused on the 135 most highly expressed transcripts. No cardiac functional data are available for almost half of these receptors; therefore, linking GPCR expression patterns to cardiac function has allowed us to provide new insights into the possible function of some of these receptors. Indeed, ventricles and atria are both contractile; however, the latter, and especially the right atrium, are central to the generation and regulation of cardiac rhythm. Accordingly, the right atrium exhibited the most specific signature, whereas the majority of GPCRs found in ventricles were evenly expressed in both the right and left chambers. RT-PCR data were confirmed at the protein level for six selected transcripts. Furthermore, we provide new data showing that, as suggested by our repertoire, the metabotropic glutamate receptor 1b is expressed and is functional in ventricular cardiac myocytes. This is the first report describing GPCRs in the four cardiac chambers and may assist in the identification of therapeutic targets.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut National de la Santé et de la Recherche Médicale U661, Université de Montpellier 1, 2, Montpellier, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moore-Morris
authors.forename: Annie
authors.initials: A
authors.lastname: Varrault
authors.forename: Matteo E
authors.initials: ME
authors.lastname: Mangoni
authors.forename: Anne
authors.initials: A
authors.lastname: Le Digarcher
authors.forename: Vincent
authors.initials: V
authors.lastname: Negre
authors.forename: Christelle
authors.initials: C
authors.lastname: Dantec
authors.forename: Laurent
authors.initials: L
authors.lastname: Journot
authors.forename: Joel
authors.initials: J
authors.lastname: Nargeot
authors.forename: Brigitte
authors.initials: B
authors.lastname: Couette
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020869:Gene Expression Profiling; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics; D012118:Resorcinols / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; C079215:3,5-dihydroxyphenylglycine; D002118:Calcium; D005998:Glycine