TY - CHAP
T1 - Sensing Extracellular Calcium – An Insight into the Structure and Function of the Calcium-Sensing Receptor (CaSR)
AU - Chavez-Abiega, Sergei
AU - Mos, Iris
AU - Centeno, Patricia P.
AU - Elajnaf, Taha
AU - Schlattl, Wolfgang
AU - Ward, Donald T.
AU - Goedhart, Joachim
AU - Kallay, Enikö
PY - 2020
Y1 - 2020
N2 - The calcium-sensing receptor (CaSR) is a G protein-coupled receptor that plays a key role in calcium homeostasis, by sensing free calcium levels in blood and regulating parathyroid hormone secretion in response. The CaSR is highly expressed in parathyroid gland and kidney where its role is well characterised, but also in other tissues where its function remains to be determined. The CaSR can be activated by a variety of endogenous ligands, as well as by synthetic modulators such as Cinacalcet, used in the clinic to treat secondary hyperparathyroidism in patients with chronic kidney disease. The CaSR couples to multiple G proteins, in a tissue-specific manner, activating several signalling pathways and thus regulating diverse intracellular events. The multifaceted nature of this receptor makes it a valuable therapeutic target for calciotropic and non-calciotropic diseases. It is therefore essential to understand the complexity behind the pharmacology, trafficking, and signalling characteristics of this receptor. This review provides an overview of the latest knowledge about the CaSR and discusses future hot topics in this field.
AB - The calcium-sensing receptor (CaSR) is a G protein-coupled receptor that plays a key role in calcium homeostasis, by sensing free calcium levels in blood and regulating parathyroid hormone secretion in response. The CaSR is highly expressed in parathyroid gland and kidney where its role is well characterised, but also in other tissues where its function remains to be determined. The CaSR can be activated by a variety of endogenous ligands, as well as by synthetic modulators such as Cinacalcet, used in the clinic to treat secondary hyperparathyroidism in patients with chronic kidney disease. The CaSR couples to multiple G proteins, in a tissue-specific manner, activating several signalling pathways and thus regulating diverse intracellular events. The multifaceted nature of this receptor makes it a valuable therapeutic target for calciotropic and non-calciotropic diseases. It is therefore essential to understand the complexity behind the pharmacology, trafficking, and signalling characteristics of this receptor. This review provides an overview of the latest knowledge about the CaSR and discusses future hot topics in this field.
KW - Allosteric modulators
KW - Biased signalling
KW - Calcilytics
KW - Calcimimetics
KW - Cellular trafficking
KW - Extracellular calcium
KW - G protein-coupled receptor
KW - G proteins
KW - Orthosteric ligands
KW - Parathyroid hormone
UR - http://www.scopus.com/inward/record.url?scp=85074068730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074068730&partnerID=8YFLogxK
U2 - 10.1007/978-3-030-12457-1_41
DO - 10.1007/978-3-030-12457-1_41
M3 - Chapter
C2 - 31646544
AN - SCOPUS:85074068730
SN - 9783030124564
T3 - Advances in Experimental Medicine and Biology
SP - 1031
EP - 1063
BT - Calcium Signaling
A2 - Islam, Shahidul
PB - Springer Nature Switzerland AG
CY - Cham
ER -
