Calcium-sensing receptor
The calcium-sensing receptor (CaSR) is a Class C 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
The release of PTH is inhibited in response to elevations in plasma calcium concentrations and activation of the calcium receptor. Decreased calcium binding on the extracellular side gives a conformational 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 a CaSR gene cause Familial hypocalciuric hypercalcemia (FHH) (also known as Familial Benign Hypercalcemia because it is generally asymptomatic and does not require treatment),[5] when present in heterozygotes. Patients who are homozygous for CaSR inactivating mutations have more severe hypercalcemia.[6] Other mutations that activate CASR are the cause of autosomal dominant hypocalcemia[7] 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.[8]
Therapeutic application
The drug cinacalcet is an allosteric modifier of the calcium-sensing receptor.[9] It is classified as a calcimimetic, which binds to the calcium-sensing receptor and decreases parathyroid hormone release.
Interactions
Calcium-sensing receptor has been shown to interact with Filamin.[10][11]
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). p. 260. ISBN 978-0-7817-7311-9 http://www.amazon.com/Physiology-Board-Review-Linda-Costanzo/dp/0781773113/.
{{cite book}}: Cite has empty unknown parameter:|1=(help); Missing or empty|title=(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) - ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 18328986, please use {{cite journal}} with
|pmid=18328986instead. - ^ 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=,|laysummary=, and|laysource=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help); Unknown parameter|month=ignored (help)CS1 maint: unflagged free DOI (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.
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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) - CASRdb - Calcium Sensing Receptor Database, McGill University
- 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)