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Details for receptor: CaSR

EndoNet ID: ENR01188

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  • CaSR
  • calcium-sensing receptor
  • extracellular calcium-sensing receptor
  • parathyroid cell calcium-sensing receptor
  • GPRC2A
  • PCAR1
  • CaR

General information

  • The CaR forms disulfide-linked dimers. [1]
  • The CaR is a G protein-coupled receptor in the same subfamily C as the metabotropic glutamate receptors, mGluRs1-8. [1]
  • Stimulation of CaR by an increase in the extracellular Ca(2+) concentration leads to periodic synthesis of inositol 1,4,5-trisphosphate, whereas l-phenylalanine stimulation of the CaR does not induce any detectable change in the level this second messenger. [2]
  • Calcium-sensing receptors (CaR) regulate cell proliferation, differentiation, and apoptosis through the MAPK pathway. [3]
  • The extracellular calcium (Ca2+)-sensing receptor plays a key role in mineral ion homeostasis by sensing small perturbations in the level of Ca2+ and modulating the functions of parathyroid and kidney so as to restore Ca2+ to its normal level. [1]
  • CaR can function as a stereoselective receptor for aromatic and other L-amino acids. [1]

Links to other resources

UniProt P41180
Ensembl ENST00000360387

Binding hormones

  • calcium ions
  • phenylalanine
    • Phenylalanine binds to the CaR in its ECD. [1]

Anatomical structures with this receptor

  • monocyte

    Induced phenotypes

    • cytokine secretion
      • The activation of CaSR increases intracellular calcium levels through Gq-PLC-Triphosphate (IP3) pathways and commits to cytokine secretion. [4]
  • colon

    Induced phenotypes

    • colonocyte differentiation
      • The CaSR plays an important role in the proliferation and differentiation of colonocytes. [5]
      • The CaSR promotes the expression of E-cadherin and suppresses the activation of ß-catenin/ TCF factor, therby regulating the differentiation of colonic epithelial cells. [6]
  • large_intestine

  • hypothalamus

  • kidney

    Induced phenotypes

    • inhibition of the reabsorption of renal mineral ions
      • The CaSR has an inhibitory effect on the reabsorption of calcium, potassium, sodium and water in all nephron segments except for the proximal tube. [7]
  • mammary_gland


    • negative PTH
      • The CaR is expressed prominently in the parathyroid gland and in the kidney, and activation of the receptor by increased Ca2+ suppresses PTH secretion and increases renal calcium excretion [8]
    • negative PTHLH
      • The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that signals in response to extracellular calcium and regulates parathyroid hormone secretion. The CaR is also expressed on normal mammary epithelial cells (MMECs), where it has been shown to inhibit secretion of parathyroid hormone-related protein (PTHrP) and participate in the regulation of calcium and bone metabolism during lactation. [8]
    • positive ACTH
      • CaSR activation led to the stimulation of cAMP production, and PTHrP and ACTH secretion from these cells. [9]
  • thyroid_gland

    Induced phenotypes

    • regulation of serum calcium levels
      • G protein-coupled extracellular calcium-sensing receptor regulates serum calcium levels by parathyroid hormone and calcitonin. [10]
      • G protein-coupled extracellular calcium-sensing receptor plays central role in calcium homeostasis by recognizing and responding to small changes in extracellular calcium, modulates functions of CaSR-expressing cells as to normalize the level of extracellular calcium. [11]
    • stimulation of phospholipase activity
      • G protein-coupled extracellular calcium-sensing receptor stimulates phospholipase C, A2, and D. [12]
    • inhibition of adenylate cyclase activity by G-protein signaling pathway
      • G protein-coupled extracellular calcium-sensing receptor inhibits adenylate cyclase through pertussis toxin-sensitive and -insensitive mechanisms. [11]
    • activation of MAPK cascade
      • G protein-coupled extracellular calcium-sensing receptor activates several mitogen-activated protein kinase (MAPK) cascades. [13]
    • neonatal hyperparathyroidism
      • Extracellular calcium ions are recognized as principal physiological regulators of parathyroid hormone secretion acting to close a endocrine feedback loop, whereby parathyroid hormone elevates extracellular calcium and in turn elevated extracellular calium suppresses parathyroid hormone secretion. [14]
      • Targeted deletion of CaSR eliminates feedback control of parathyroid hormone secretion and results in severe form of neonatal hyperparathyroidism. [14]
  • parathyroid_gland


    • negative PTH
      • in physiological concentrations, L-amino acids acutely and reversibly activated the extracellular Ca2+-sensing receptor in normal human parathyroid cells and inhibited parathyroid hormone secretion. [15]
      • Parathormone (PTH) secretion from the parathyroid gland is suppressed by high extracellular calcium and magnesium. The calcium-sensing receptor (CaSR) is responsible for the calcium-dependent inhibition of PTH secretion. [16]
      • L-amino acids are physiological regulators of PTH secretion and thus whole body calcium metabolism. [15]
      • In the parathyroid gland, the CaSR mediates low extracellular calium-evoked increases in secretion of the extracellular calium-elevating hormone, parathyroid hormone, as well as in parathyroid cellular proliferation..22.9 [11]

    Induced phenotypes

    • Familial benign hypocalciuric hypercalcemia
      • FBHH/FHH, transmitted in an autosomal dominant fashion, is due in most, but not all, cases to a heterozygous mutation in the calcium-sensing receptor (CaSR) gene that is the main regulator of parathyroid cell responsivity to calcium. [17]
  • fat_cell

    Induced phenotypes

    • regulation of lipid biosynthetic process
      • CaSR signaling could be plausible related to proliferation, differentiation, and metabolic activity of adipose cells. Activation of the receptor in the adipocyte is expected to trigger signaling cascades, that have been described in relevant phenomena in adipocyte metabolism such as adipogenesis and lipogenesis. [18]
    • inhibition of lipolysis
      • The CaSR displays an inhibitory effect on lipolysis by mediating intracellular cAMP and calcium levels causing the downregulation of downstream key enzymes of lipolysis (i.e. HSL and ATGL). [19]
  • astrocyte

    Induced phenotypes

    • astrocyte differentiation
      • CaSR regulates the differentiation of astrocyte by stimulating the release of parathyroid hormone-related prootein (PTHrP). [20]
  • epithelial_cell

  • keratinocyte

    Induced phenotypes

    • keratinocyte differentiation
      • Epidermal expression of CaSR is required for the terminal differentiation of keratinocytes mediated by the stringent control of extracellular calcium levels. [21]
  • glial_cell_of_central_nervous_system

  • enteric_glial_cell

  • retinal_pigment_epithelium_RPE

  • lymphoblast

  • osteocyte

    Induced phenotypes

    • bone cell metabolism
      • The CaSR regulates the recruitment, differentiation and survival of osteoblast and osteoclasts. [22]
  • neuron

    Induced phenotypes

    • growth of neuronal processes
      • The CaSR regulates the growth of neuronal processes both in the peripheral and central nervous system and may thus participate in processes underlying learning and memory. [23]
    • regulation of myelination
      • Functional CaSRs are expressed in mature oligodendrocytes pointing to a potential role in myelination. [24]
  • osteoclast

    Induced phenotypes

    • regulation of bone resorption
      • The activation of CaSR leads to the down-regulation of osteoclastic activity. [25]
  • pancreas

    Induced phenotypes

    • regulation of serum calcium levels
      • The CasR regulates the calcium concentration in the pancreatic juice by triggering ductal electrolyte and fluid secretion. [26]
    • regulation of pancreatic ductal cells
      • The activation of CaSR causes the decrease of pancreatic ductal cell proliferation (elvated extracellular Ca2+). [26]
  • enterochromaffin_like_cell

  • G_cell


    • gastrin
  • digestive_system

  • beta_cell_of_islet_of_Langerhans


    • positive insulin
      • The extracellular, G protein-linked Ca21-sensing receptor (CaSR), first identified in the parathyroid gland, is expressed in several tissues and cells and can be activated by Ca21 and some other inorganic cations and organic polycations; and stimulate insulin secretion in beta-cells. [10]
  • Goormaghtighs_cell


    • negative renin
      • CaSRs modulate renin release both in vitro and in vivo. CaSRs play a role as a regulatory pathway of renin release. [27]
      • Activation of CaSR significantly decreases both JG cell cAMP formation and renin release by ~45%. Juxtaglomerular cells express CaSR, and CaSR respond to changes in extracellular calcium to modify or activate calcium-mediated intracellular signaling. [28]
      • While calcium does not directly control renin secretion, increased calcium inhibits and decreased calcium amplifies cAMP-stimulated renin secretion. [29]