Implications of the calcium-sensing receptor in ischemia/reperfusion. Issue 2 (4th March 2017)

• Record Type: Journal Article
• Authors: Paquot, François; Huart, Justine; Defraigne, Jean-Olivier; Krzesinski, Jean-Marie; Jouret, François
• Is Part Of: Acta cardiologica. Volume 72:Issue 2(2017)
• Page Start: 125
• Page End: 131
• Publication Date: 2017-03-04
• Subjects: Calcium-sensing receptor -- ischaemia/reperfusion injury -- therapeutic hypothermia -- apoptosis -- ischaemic conditioning; Cardiology -- Periodicals; Cardiology; Cardiologie -- Périodiques; Cardiology; Cardiologie; Periodicals; Periodicals; 616.12005
• DOI: 10.1080/00015385.2017.1291136
• Languages: English
• ISSNs: 0001-5385

Abstract

Abstract: The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) which was first isolated from bovine parathyroid glands. Its complex structure has been well characterized, which helped to better understand its function. The CaSR activity can be modulated by various ligands, either activators (also called "calcimimetics") or inhibitors (or "calcilytics"). The main role of the CaSR concerns Ca 2+ homeostasis. In bone, intestine and kidney, the CaSR acts as a sensor for extracellular ionized Ca 2+ concentration ([Ca 2+ ]e ) to keep it stable. Such a homeostatic function is well illustrated by human inherited diseases caused by mutations in CASR gene, characterized by Ca 2+ balance disturbances. Interestingly, the CaSR is also expressed in numerous tissues which are not directly involved in Ca 2+ regulation. There, the CaSR has been implicated in regulatory pathways, including cell proliferation, differentiation and apoptosis. Moreover, recent observations suggest that the CaSR may be involved in ischaemia/reperfusion (I/R) cascades. In cardiomyocytes, the expression and activation of the CaSR are significantly induced at the time of I/R, which induces apoptotic pathways. Likewise, the activation of the CaSR in I/R in brain, liver and kidney has been associated with increased cell death and aggravated structural and functional damage. The present review summarizes these observations and hypothesizes a novel therapeutic option targeting the CaSR in I/R.