Abstract 3438: Gene Expression Profiling of G Protein-Coupled Receptors in the Adult Mouse Heart
The G protein-coupled receptors (GPCRs), one of the major targets of pharmaceutical drugs, are essential to many aspects of heart physiology including the regulation of heart rate, contractile force, cardiac remodelling and gene expression. The present study addresses the expression of endoGPCRs, all GPCRs excluding taste and odorant receptors, in each of the four cardiac chambers of adult mouse heart. High-throughput real-time RT-PCR was used to quantify 396 GPCRs and 7 associated proteins in right and left atria and ventricles. Statistical analysis of the most highly expressed transcripts showed that 47 were equally expressed throughout the heart and 89 were differentially expressed in at least one cardiac chamber. Among receptors uniformly expressed, we found well-characterized receptors such as the β2 adrenergic receptor, muscarinic M2 receptor, endothelin receptor type A (ETA) and purinoceptor P2Y2. Surprisingly enough, many of the most abundantly expressed GPCRs (e.g. belonging to the frizzled or chemokine receptor subfamilies) had not previously been identified in healthy heart. Repertoire analysis revealed genes specific to atria and ventricles. The atria exhibited the most specific signature with a lot of receptors not yet studied (receptors belonging to the EGF-like, Mucin-like, Decay-accelerating Factor and Mas-related subfamilies). No gene appeared to be significantly specific to the left or right side of the heart. RT-PCR data were confirmed at the protein level in all four cavities for several receptors and regulatory proteins including ETA, angiotensin receptor 1, protease-activated receptor 1, chemokine receptor CCR2, secreted frizzled related protein 1 and metabotropic glutamate receptor 1 (mGluR1). We also demonstrate that the mGluR1b splice variant is the sole highly expressed metabotropic glutamate receptor in adult mouse heart and is present and functional in isolated ventricular cardiomyocytes. Thus, large scale identification of the regional expression pattern of GPCRs in normal, and in the future in pathological conditions, might lead to the identification of new pharmacological targets for the treatment of human heart diseases.