The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that senses extracellular Ca2+. The CaSR has wide tissue expression being found in the parathyroid gland, thyroid, kidney, intestine, skin, brain, heart, pancreas, bone and lung. First cloned from the bovine parathyroid gland in 1993, the primary role of CaSR activation is the inhibition of the release of parathyroid hormone (PTH).
CaSRs can also work independently of PTH. Local changes in extracellular Ca2+ regulate the differentiation and function of chondrocytes, osteoclasts and osteoblasts in bone function, potentially via the CaSR. It also has been implicated in the calcium absorption in the gastrointestinal system and in synaptic transmission.
The CaSR has also been implicated in numerous signal transduction pathways. Decreased binding of extracellular Ca2+ leads to conformational changes in the CaSR, initiating the phospholipase C pathway. Activation of CaSRs also inhibits adenylyl cyclase and suppresses intracellular cAMP, inhibiting cAMP-dependent pathways.
Mutations of the CaSR gene can lead to calcium related disorders such as familial hypocalciuric hypercalcemia.
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