Calcium-sensing receptor: Difference between revisions
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The drug [[cinacalcet]] is an [[allosteric]] modifier of the calcium-sensing receptor.<ref name="pmid16825031">{{cite journal | author = Torres PU | title = Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease | journal = Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation | volume = 16 | issue = 3 | pages = 253–8 | year = 2006 | pmid = 16825031 | doi = 10.1053/j.jrn.2006.04.010 | issn = }}</ref> |
The drug [[cinacalcet]] is an [[allosteric]] modifier of the calcium-sensing receptor.<ref name="pmid16825031">{{cite journal | author = Torres PU | title = Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease | journal = Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation | volume = 16 | issue = 3 | pages = 253–8 | year = 2006 | pmid = 16825031 | doi = 10.1053/j.jrn.2006.04.010 | issn = }}</ref> |
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==Interactions== |
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Calcium-sensing receptor has been shown to [[Protein-protein_interaction|interact]] with [[Filamin]].<ref name=pmid11390380>{{cite journal | quotes = yes |last=Hjälm |first=G |authorlink= |coauthors=MacLeod R J, Kifor O, Chattopadhyay N, Brown E M |year=[[2001]]|month=Sep. |title=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 |journal=J. Biol. Chem. |volume=276 |issue=37 |pages=34880-7 |publisher= |location = United States| issn = 0021-9258| pmid = 11390380 |doi = 10.1074/jbc.M100784200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref><ref name=pmid11390379>{{cite journal | quotes = yes |last=Awata |first=H |authorlink= |coauthors=Huang C, Handlogten M E, Miller R T |year=[[2001]]|month=Sep. |title=Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein |journal=J. Biol. Chem. |volume=276 |issue=37 |pages=34871-9 |publisher= |location = United States| issn = 0021-9258| pmid = 11390379 |doi = 10.1074/jbc.M100775200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref> |
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==References== |
==References== |
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{{Reflist|2}} |
{{Reflist|2}} |
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Revision as of 17:56, 20 July 2009
The calcium-sensing receptor (CaSR) is a G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone (PTH).[1]
Signal transduction
Binding to calcium on the extracellular side gives a conformation change in the receptor, which, on the intracellular side, initiates the phospholipase C pathway,[2][3] presumably through a Gqα type of G protein, which ultimately increases intracellular concentration of calcium, which triggers vesicle fusion and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some[4] sources state) the cAMP dependent pathway.[3]
Pathology
Mutations that inactivate CASR cause familial hypocalciuric hypercalcemia (FHH) (also known as Familial Benign Hypercalcemia because it is generally asymptomatic and does not require treatment),[5] whereas mutations that activate CASR are the cause of autosomal dominant hypocalcemia.[6] An alternatively spliced transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.[7]
Therapeutic application
The drug cinacalcet is an allosteric modifier of the calcium-sensing receptor.[8]
Interactions
Calcium-sensing receptor has been shown to interact with Filamin.[9][10]
References
- ^ D'Souza-Li L (2006). "The calcium-sensing receptor and related diseases". Arquivos brasileiros de endocrinologia e metabologia. 50 (4): 628–39. doi:10.1590/S0004-27302006000400008. PMID 17117288.
- ^ 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 (1999). "Calcium-sensing receptor and calcimimetic agents". Kidney Int. Suppl. 73: S52–8. PMID 10633465.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Costanzo, Linda S. (2007). BRS Physiology. Lippincott, Williams, & Wilkins. p. 260. ISBN 978-0781773119.
{{cite book}}: Cite has empty unknown parameter:|coauthors=(help) - ^ Pidasheva S, Canaff L, Simonds WF, Marx SJ, Hendy GN (2005). "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia". Hum. Mol. Genet. 14 (12): 1679–90. doi:10.1093/hmg/ddi176. PMID 15879434.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Mancilla EE, De Luca F, Baron J (1998). "Activating mutations of the Ca2+-sensing receptor". Mol. Genet. Metab. 64 (3): 198–204. doi:10.1006/mgme.1998.2716. PMID 9719629.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "Entrez Gene: CASR calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)".
- ^ Torres PU (2006). "Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease". Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 16 (3): 253–8. doi:10.1053/j.jrn.2006.04.010. PMID 16825031.
- ^ Hjälm, G (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". J. Biol. Chem. 276 (37). United States: 34880–7. doi:10.1074/jbc.M100784200. ISSN 0021-9258. PMID 11390380.
{{cite journal}}: Check date values in:|year=(help); Cite has empty unknown parameters:|laydate=,|laysource=, and|laysummary=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help); Unknown parameter|month=ignored (help); Unknown parameter|quotes=ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link) - ^ Awata, H (2001). "Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein". J. Biol. Chem. 276 (37). United States: 34871–9. doi:10.1074/jbc.M100775200. ISSN 0021-9258. PMID 11390379.
{{cite journal}}: Check date values in:|year=(help); Cite has empty unknown parameters:|laydate=,|laysource=, and|laysummary=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help); Unknown parameter|month=ignored (help); Unknown parameter|quotes=ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link)
Further reading
External links
- "Calcium-Sensing Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help) - Receptors,+Calcium-Sensing at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- CASR+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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