同: Ca sensing receptor

同: calcium-sensing receptor

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Calciumの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/08/28 20:54:51」(JST)

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The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. It is primarily expressed in the parathyroid gland and the renal tubules of the kidney. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone (PTH).^[5] In the kidney it has an inhibitory effect on the reabsorption of calcium, potassium, sodium, and water depending on which segment of the tubule is being activated.^[6]

Signal transduction

The release of PTH is inhibited in response to elevations in plasma calcium concentrations and activation of the calcium receptor. Increased calcium binding on the extracellular side gives a conformational change in the receptor, which, on the intracellular side, initiates the phospholipase C pathway,^[7]^[8] presumably through a G_qα type of G protein, which ultimately increases intracellular concentration of calcium, which inhibits vesicle fusion and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some^[9] sources state) the cAMP dependent pathway.^[8]

Pathology

Mutations that inactivate a CaSR gene cause familial hypocalciuric hypercalcemia (FHH) (also known as familial benign hypercalcemia because it is generally asymptomatic and does not require treatment),^[10] when present in heterozygotes. Patients who are homozygous for CaSR inactivating mutations have more severe hypercalcemia.^[11] Other mutations that activate CaSR are the cause of autosomal dominant hypocalcemia^[12] or Type 5 Bartter syndrome. An alternatively spliced transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.^[13]

Therapeutic application

The drugs cinacalcet and etelcalcetide are allosteric modifiers of the calcium-sensing receptor.^[14] They are classified as a calcimimetics, binding to the calcium-sensing receptor and decreasing parathyroid hormone release.

Calcilytic drugs, which block CaSR, produce increased bone density in animal studies and have been researched for the treatment of osteoporosis. Unfortunately clinical trial results in humans have proved disappointing, with sustained changes in bone density not observed despite the drug being well tolerated.^[15]^[16] More recent research has shown the CaSR receptor to be involved in numerous other conditions including Alzheimer's disease, asthma and some forms of cancer,^[17]^[18]^[19]^[19]^[20] and calcilytic drugs are being researched as potential treatments for these.

Interactions

Calcium-sensing receptor has been shown to interact with filamin.^[21]^[22]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000036828 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000051980 - Ensembl, May 2017
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ D'Souza-Li L (Aug 2006). "The calcium-sensing receptor and related diseases". Arquivos Brasileiros de Endocrinologia e Metabologia. 50 (4): 628–39. PMID 17117288. doi:10.1590/S0004-27302006000400008.
^ Vezzoli, Giuseppe; Soldati, Laura; Gambaro, Giovanni (2009-04-01). "Roles of calcium-sensing receptor (CaSR) in renal mineral ion transport". Current Pharmaceutical Biotechnology. 10 (3): 302–310. ISSN 1873-4316. PMID 19355940.
^ InterPro: IPR000068 GPCR, family 3, extracellular calcium-sensing receptor-related Retrieved on June 2, 2009
^ ^a ^b Coburn JW, Elangovan L, Goodman WG, Frazaõ JM (Dec 1999). "Calcium-sensing receptor and calcimimetic agents". Kidney International. Supplement. 73: S52–8. PMID 10633465.
^ Costanzo, Linda S. (2007). BRS Physiology (Board Review Series). p. 260. ISBN 978-0-7817-7311-9.
^ Pidasheva S, Canaff L, Simonds WF, Marx SJ, Hendy GN (Jun 2005). "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia". Human Molecular Genetics. 14 (12): 1679–90. PMID 15879434. doi:10.1093/hmg/ddi176.
^ Egbuna OI, Brown EM (Mar 2008). "Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations". Best Practice & Research. Clinical Rheumatology. 22 (1): 129–148. PMC 2364635 . PMID 18328986. doi:10.1016/j.berh.2007.11.006.
^ Mancilla EE, De Luca F, Baron J (Jul 1998). "Activating mutations of the Ca2+-sensing receptor". Molecular Genetics and Metabolism. 64 (3): 198–204. PMID 9719629. doi:10.1006/mgme.1998.2716.
^ "Entrez Gene: CaSR calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)".
^ Torres PU (Jul 2006). "Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease". Journal of Renal Nutrition. 16 (3): 253–8. PMID 16825031. doi:10.1053/j.jrn.2006.04.010.
^ Nemeth EF, Shoback D (Jun 2013). "Calcimimetic and calcilytic drugs for treating bone and mineral-related disorders". Best Practice & Research. Clinical Endocrinology & Metabolism. 27 (3): 373–84. PMID 23856266. doi:10.1016/j.beem.2013.02.008.
^ John MR, Harfst E, Loeffler J, Belleli R, Mason J, Bruin GJ, Seuwen K, Klickstein LB, Mindeholm L, Widler L, Kneissel M (Jul 2014). "AXT914 a novel, orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women". Bone. 64: 204–10. PMID 24769332. doi:10.1016/j.bone.2014.04.015.
^ Kim JY, Ho H, Kim N, Liu J, Tu CL, Yenari MA, Chang W (Nov 2014). "Calcium-sensing receptor (CaSR) as a novel target for ischemic neuroprotection". Annals of Clinical and Translational Neurology. 1 (11): 851–66. PMC 4265057 . PMID 25540800. doi:10.1002/acn3.118.
^ Aggarwal A, Prinz-Wohlgenannt M, Tennakoon S, Höbaus J, Boudot C, Mentaverri R, Brown EM, Baumgartner-Parzer S, Kállay E (Feb 2015). "The calcium-sensing receptor: A promising target for prevention of colorectal cancer". Biochimica et Biophysica Acta. 1853: 2158–67. PMC 4549785 . PMID 25701758. doi:10.1016/j.bbamcr.2015.02.011.
^ ^a ^b Dal Prà I, Chiarini A, Armato U (Feb 2015). "Antagonizing amyloid-β/calcium-sensing receptor signaling in human astrocytes and neurons: a key to halt Alzheimer's disease progression?". Neural Regeneration Research. 10 (2): 213–8. PMC 4392667 . PMID 25883618. doi:10.4103/1673-5374.152373.
^ Yarova PL, Stewart AL, Sathish V, Britt RD, Thompson MA, P Lowe AP, Freeman M, Aravamudan B, Kita H, Brennan SC, Schepelmann M, Davies T, Yung S, Cholisoh Z, Kidd EJ, Ford WR, Broadley KJ, Rietdorf K, Chang W, Bin Khayat ME, Ward DT, Corrigan CJ, T Ward JP, Kemp PJ, Pabelick CM, Prakash YS, Riccardi D (Apr 2015). "Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma". Science Translational Medicine. 7 (284): 284ra60. PMC 4725057 . PMID 25904744. doi:10.1126/scitranslmed.aaa0282.
^ Hjälm G, MacLeod RJ, Kifor O, Chattopadhyay N, Brown EM (Sep 2001). "Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase". The Journal of Biological Chemistry. 276 (37): 34880–7. PMID 11390380. doi:10.1074/jbc.M100784200.
^ Awata H, Huang C, Handlogten ME, Miller RT (Sep 2001). "Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein". The Journal of Biological Chemistry. 276 (37): 34871–9. PMID 11390379. doi:10.1074/jbc.M100775200.

External links

"Calcium-Sensing Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
CASRdb - Calcium Sensing Receptor Database, McGill University
Receptors, Calcium-Sensing at the US National Library of Medicine Medical Subject Headings (MeSH)
CASR protein at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. カルシウム感知性受容体障害：家族性低カルシウム尿性高カルシウム血症および常染色体優性低カルシウム血症 disorders of the calcium sensing receptor familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia
2. 副甲状腺ホルモンの分泌および作用 parathyroid hormone secretion and action
3. カルシウムおよびリン酸バランスの調節 regulation of calcium and phosphate balance
4. 原発性副甲状腺機能亢進症の発症機序および病因 pathogenesis and etiology of primary hyperparathyroidism
5. バーター症候群およびギテルマン症候群 bartter and gitelman syndromes

English Journal

An examination of the environmental, driver and vehicle factors associated with the serious and fatal crashes of older rural drivers.

Thompson JP, Baldock MR, Mathias JL, Wundersitz LN.SourceCentre for Automotive Safety Research, The University of Adelaide, SA 5005, Australia; School of Psychology, The University of Adelaide, SA 5000, Australia. Electronic address: james@casr.adelaide.edu.au.
Accident; analysis and prevention.Accid Anal Prev.2013 Jan;50:768-75. doi: 10.1016/j.aap.2012.06.028. Epub 2012 Jul 18.
Motor vehicle crashes involving rural drivers aged 75 years and over are more than twice as likely to result in a serious or fatal injury as those involving their urban counterparts. The current study examined some of the reasons for this using a database of police-reported crashes (2004-2008) to id
PMID 22818779

An efficient Escherichia coli expression system for the production of a functional N-terminal domain of the T1R3 taste receptor.

Maîtrepierre E, Sigoillot M, Le Pessot L, Briand L.SourceCentre des Sciences du Goût et de l'Alimentation, UMR-1324 INRA, UMR-6265 CNRS, Université de Bourgogne, 21000 Dijon, France.
Bioengineered.Bioengineered.2013 Jan 1;4(1). [Epub ahead of print]
Sweet taste is mediated by a dimeric receptor composed of two distinct subunits, T1R2 and T1R3, whereas the T1R1/T1R3 receptor is involved in umami taste perception. The T1R1, T1R2, and T1R3 subunits are members of the small family of class C G protein-coupled receptors (GPCRs). The members of this
PMID 22909933

Japanese Journal

Pathological function of Ca2+-sensing receptor in pulmonary arterial hypertension

Yamamura Aya
Journal of Smooth Muscle Research 50(0), 8-17, 2014
… We recently found that the extracellular Ca2+-sensing receptor (CaSR), which belongs to family C of the G protein-coupled receptor (GPCR) superfamily, is upregulated in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH). … The upregulated CaSR is necessary for the enhanced Ca2+ signaling and the augmented cell proliferation in PASMCs from IPAH patients. …
NAID 130003391244

副甲状腺機能低下症および偽性副甲状腺機能低下症 (特集知っておきたい先天性・遺伝性内分泌疾患)

難波範行
内分泌・糖尿病・代謝内科 37(4), 373-379, 2013-10
NAID 40019847614

カルシウム感知受容体(CaSR)アゴニストとして発見された「コク味」物質による風味の修飾

幸田徹
バイオサイエンスとインダストリー = Bioscience & industry 71(3), 210-214, 2013-05-01
NAID 10031166365

Related Pictures

Conexiones Circulares → Conexion CASR CASR/CSMR Schematic model for CaSR signaling and its 모던 가죽케이스 CASR-011B(블랙 fotos de maduras casr Best first casr maserati grancabrio Y8 maserati casr Wallpaper Abbildung 1: CaSR

★リンクテーブル★

リンク元	「カルシウム感知受容体」「calcium-sensing receptor」
関連記事	「Ca」

「カルシウム感知受容体」

CASR
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	5FBH, 5FBK
Identifiers
Aliases	CASR, CAR, EIG8, FHH, FIH, GPRC2A, HHC, HHC1, HYPOC1, NSHPT, PCAR1, calcium sensing receptor, hCasR, Calcium-sensing receptor+CaSR
External IDs	OMIM: 601199 MGI: 1351351 HomoloGene: 332 GeneCards: CASR
Gene location (Human)
Chr.	Chromosome 3 (human)
End	122,291,629 bp
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)
End	36,562,141 bp
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• protein binding; • signal transducer activity; • phosphatidylinositol phospholipase C activity; • G-protein coupled receptor activity; • amino acid binding; • protein homodimerization activity; • metal ion binding; • magnesium ion binding; • integrin binding; • calcium ion binding; • drug binding; • polyamine binding; • protein kinase binding; • ion channel binding;
Cellular component	• integral component of membrane; • plasma membrane; • membrane; • integral component of plasma membrane; • nucleus; • cytoplasm; • cell surface; • basolateral plasma membrane; • apical plasma membrane; • axon; • neuron projection; • neuronal cell body; • axon terminus;
Biological process	• chemosensory behavior; • calcium ion import; • anatomical structure morphogenesis; • signal transduction; • detection of calcium ion; • G-protein coupled receptor signaling pathway; • ossification; • response to ischemia; • calcium ion transport; • cellular calcium ion homeostasis; • apoptotic process; • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway; • phospholipase C-activating G-protein coupled receptor signaling pathway; • JNK cascade; • positive regulation of cell proliferation; • response to metal ion; • positive regulation of gene expression; • response to organic cyclic compound; • positive regulation of insulin secretion; • positive regulation of ATPase activity; • cellular response to hepatocyte growth factor stimulus; • vasodilation; • positive regulation of vasoconstriction; • branching morphogenesis of an epithelial tube; • positive regulation of positive chemotaxis; • response to calcium ion; • regulation of calcium ion transport; • fat pad development; • cellular response to vitamin D; • cellular response to glucose stimulus; • cellular response to low-density lipoprotein particle stimulus; • cellular response to hypoxia; • response to fibroblast growth factor; • positive regulation of calcium ion import; • cellular response to peptide;
	Sources:Amigo / QuickGO
Orthologs
	846
	12374
	ENSG00000036828
	ENSMUSG00000051980
	P41180
	Q9QY96
	NM_000388; NM_001178065
	NM_013803
	NP_000379; NP_001171536
	NP_038831
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

英: calcium-sensing receptor CaR CaSR
同: カルシウム感知性受容体、カルシウム感受受容体、カルシウム感受性受容体、カルシウム受容体、Ca感知受容体
関: 副甲状腺、カルシウム

Ca2+と結合

副甲状腺：PTHの分泌のフィードバック制御
腎尿細管：カルシウム吸収の制御

「calcium-sensing receptor」

　　[★]

カルシウム感知受容体

関: calcium receptor

同: CaSR

「Ca」

　　[★] カルシウム calcium 　

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000036828 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000051980 - Ensembl, May 2017

[3] "Human PubMed Reference:".

[4] "Mouse PubMed Reference:".

[pmid17117288-5] D'Souza-Li L (Aug 2006). "The calcium-sensing receptor and related diseases". Arquivos Brasileiros de Endocrinologia e Metabologia. 50 (4): 628–39. PMID 17117288. doi:10.1590/S0004-27302006000400008.

[6] Vezzoli, Giuseppe; Soldati, Laura; Gambaro, Giovanni (2009-04-01). "Roles of calcium-sensing receptor (CaSR) in renal mineral ion transport". Current Pharmaceutical Biotechnology. 10 (3): 302–310. ISSN 1873-4316. PMID 19355940.

[7] InterPro: IPR000068 GPCR, family 3, extracellular calcium-sensing receptor-related Retrieved on June 2, 2009

[coburn-8] Coburn JW, Elangovan L, Goodman WG, Frazaõ JM (Dec 1999). "Calcium-sensing receptor and calcimimetic agents". Kidney International. Supplement. 73: S52–8. PMID 10633465.

[brs-9] Costanzo, Linda S. (2007). BRS Physiology (Board Review Series). p. 260. ISBN 978-0-7817-7311-9.

[pmid15879434-10] Pidasheva S, Canaff L, Simonds WF, Marx SJ, Hendy GN (Jun 2005). "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia". Human Molecular Genetics. 14 (12): 1679–90. PMID 15879434. doi:10.1093/hmg/ddi176.

[11] Egbuna OI, Brown EM (Mar 2008). "Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations". Best Practice & Research. Clinical Rheumatology. 22 (1): 129–148. PMC 2364635 . PMID 18328986. doi:10.1016/j.berh.2007.11.006.

[pmid9719629-12] Mancilla EE, De Luca F, Baron J (Jul 1998). "Activating mutations of the Ca2+-sensing receptor". Molecular Genetics and Metabolism. 64 (3): 198–204. PMID 9719629. doi:10.1006/mgme.1998.2716.

[13] "Entrez Gene: CaSR calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)".

[pmid16825031-14] Torres PU (Jul 2006). "Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease". Journal of Renal Nutrition. 16 (3): 253–8. PMID 16825031. doi:10.1053/j.jrn.2006.04.010.

[15] Nemeth EF, Shoback D (Jun 2013). "Calcimimetic and calcilytic drugs for treating bone and mineral-related disorders". Best Practice & Research. Clinical Endocrinology & Metabolism. 27 (3): 373–84. PMID 23856266. doi:10.1016/j.beem.2013.02.008.

[16] John MR, Harfst E, Loeffler J, Belleli R, Mason J, Bruin GJ, Seuwen K, Klickstein LB, Mindeholm L, Widler L, Kneissel M (Jul 2014). "AXT914 a novel, orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women". Bone. 64: 204–10. PMID 24769332. doi:10.1016/j.bone.2014.04.015.

[17] Kim JY, Ho H, Kim N, Liu J, Tu CL, Yenari MA, Chang W (Nov 2014). "Calcium-sensing receptor (CaSR) as a novel target for ischemic neuroprotection". Annals of Clinical and Translational Neurology. 1 (11): 851–66. PMC 4265057 . PMID 25540800. doi:10.1002/acn3.118.

[18] Aggarwal A, Prinz-Wohlgenannt M, Tennakoon S, Höbaus J, Boudot C, Mentaverri R, Brown EM, Baumgartner-Parzer S, Kállay E (Feb 2015). "The calcium-sensing receptor: A promising target for prevention of colorectal cancer". Biochimica et Biophysica Acta. 1853: 2158–67. PMC 4549785 . PMID 25701758. doi:10.1016/j.bbamcr.2015.02.011.

[ReferenceA-19] Dal Prà I, Chiarini A, Armato U (Feb 2015). "Antagonizing amyloid-β/calcium-sensing receptor signaling in human astrocytes and neurons: a key to halt Alzheimer's disease progression?". Neural Regeneration Research. 10 (2): 213–8. PMC 4392667 . PMID 25883618. doi:10.4103/1673-5374.152373.

[20] Yarova PL, Stewart AL, Sathish V, Britt RD, Thompson MA, P Lowe AP, Freeman M, Aravamudan B, Kita H, Brennan SC, Schepelmann M, Davies T, Yung S, Cholisoh Z, Kidd EJ, Ford WR, Broadley KJ, Rietdorf K, Chang W, Bin Khayat ME, Ward DT, Corrigan CJ, T Ward JP, Kemp PJ, Pabelick CM, Prakash YS, Riccardi D (Apr 2015). "Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma". Science Translational Medicine. 7 (284): 284ra60. PMC 4725057 . PMID 25904744. doi:10.1126/scitranslmed.aaa0282.

[pmid11390380-21] Hjälm G, MacLeod RJ, Kifor O, Chattopadhyay N, Brown EM (Sep 2001). "Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase". The Journal of Biological Chemistry. 276 (37): 34880–7. PMID 11390380. doi:10.1074/jbc.M100784200.

[pmid11390379-22] Awata H, Huang C, Handlogten ME, Miller RT (Sep 2001). "Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein". The Journal of Biological Chemistry. 276 (37): 34871–9. PMID 11390379. doi:10.1074/jbc.M100775200.

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CaSR