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Gene Review

Casr  -  calcium-sensing receptor

Rattus norvegicus

Synonyms: CaSR, Extracellular calcium-sensing receptor, Gprc2a, PCaR1, Parathyroid cell calcium-sensing receptor, ...
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Disease relevance of Casr


High impact information on Casr

  • METHODS: Calcium-sensing receptor activation was assessed in colonic epithelial cells and intact crypts freshly isolated from distal colon by monitoring intracellular IP(3) and Ca(2+) accumulation using radioimmunoassay and Fluo-3 fluorometry, respectively [5].
  • CaSR on nerve terminal membranes may regulate neurotransmitter disposition in response to Ca2+ levels in the synaptic space [6].
  • We have molecularly cloned a calcium sensing receptor (CaSR) from a rat striatal cDNA library [6].
  • Cerebral arteries display an intense network of CaSR immunoreactive fibers associated with vessel innervation [6].
  • Rat CaSR displays 92% overall homology to its bovine counterpart with seven putative transmembrane domains characteristic of the superfamily of guanine nucleotide-binding proteins and significant homology with the metabotropic glutamate receptors [6].

Biological context of Casr

  • 1. The DNA sequence of the DRG CaSR was 99.9% homologous with published rat kidney CaSR in the coding region and 247 bp upstream of the start site but showed little homology 5' to this site, which maps to exonic junction I/II, supporting the hypothesis that CaSR message arises as a splice variant and showing tissue-to-tissue heterogeneity [7].
  • A full-length cDNA encoding a Ca2+-sensing receptor (CaSR) expressed in rat dorsal root ganglia (DRG) was identified using rapid amplification of 5'-cDNA ends and primer extension and then cloned into the plasmid vector pCR3 [7].
  • We hypothesize that TTF-1 similarly coordinates Ca2+-dependent gene expression in all cells in which TTF-1 and the CaSR are expressed, i. e., parathyroid cells, neural cells in the anterior pituitary or hippocampus, and keratinocytes [8].
  • The calcium-sensing receptor (CaSR) is a class III G-protein-coupled receptor (GPCR) that responds to changes in extracellular calcium concentration and plays a crucial role in calcium homeostasis [9].
  • The upregulations of both VDR and CaSR, the clear shift to the left downward in the Ca(2+)-PTH curve, and the induction of apoptosis after DI-OCT were observed [3].

Anatomical context of Casr

  • Taken together, our results show that the association with RAMPs is necessary and sufficient to transfer the immature CaSR retained in the ER towards the Golgi where it becomes fully glycosylated prior to delivery to the plasma membrane and demonstrate a role for RAMPs in the trafficking of a class III GPCR [9].
  • CONCLUSION: Coexpression with SK4 potassium channels provides a fast and sensitive approach to evaluate CaSR activity in Xenopus oocytes [10].
  • To further delineate its functions in neurons and glia, we have investigated the expression pattern of CaSR transcripts in the postnatal and adult rat brain, spinal cord and dorsal root ganglia by in situ hybridization [11].
  • These data suggest that a functional CaSR is expressed in mature oligodendrocytes with a potential role in myelination [11].
  • CaSR expression was also developmentally regulated in neurons of the orbital cortex and in the CA2 region of the hippocampus, and present in olfactory nuclei, hypothalamic areas and in the area postrema through postnatal days to adulthood [11].

Associations of Casr with chemical compounds

  • Other CaSR agonists, Gd3+ and neomycin, mimicked these Ca2+(o)-induced responses [12].
  • L-Histidine (L-His) increases the sensitivity of the CaSR to extracellular Ca2+ and potentiates glucose-dependent insulin secretion from INS-1 cells [4].
  • These results indicate that CaSR monitors extracellular Mg(2+) concentration, and probably cause activation of Na(+)-independent Mg(2+)-transport system [13].
  • In the HC model, elevated renal cortex gene expression of several growth factors, peptide receptors, and intracellular signaling molecules depicts a role for CaSR activation and receptor tyrosine kinase signaling in 1,25(OH)(2)D(3)-mediated gene activation and repression of 1alpha-OHase [14].
  • By fluorophotometer (with mag-fura 2 fluorescent dye) and atomic absorption spectrophotometer, we confirmed that activation of CaSR by neomycin (0.5 mM) or gadolinium (1 mM) reinforced the decrease of [Mg(2+)](i) induced by Mg(2+) removal in the cells cultured in 10 mM Mg(2+)-containing medium [13].

Analytical, diagnostic and therapeutic context of Casr


  1. Calcium-sensing receptor induces messenger ribonucleic acid of human securin, pituitary tumor transforming gene, in rat testicular cancer. Tfelt-Hansen, J., Schwarz, P., Terwilliger, E.F., Brown, E.M., Chattopadhyay, N. Endocrinology (2003) [Pubmed]
  2. Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction. Geibel, J., Sritharan, K., Geibel, R., Geibel, P., Persing, J.S., Seeger, A., Roepke, T.K., Deichstetter, M., Prinz, C., Cheng, S.X., Martin, D., Hebert, S.C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Biochemical and cellular effects of direct maxacalcitol injection into parathyroid gland in uremic rats. Shiizaki, K., Negi, S., Hatamura, I., Sakaguchi, T., Saji, F., Kunimoto, K., Mizobuchi, M., Imazeki, I., Ooshima, A., Akizawa, T. J. Am. Soc. Nephrol. (2005) [Pubmed]
  4. Regulation of glucagon-like peptide-1 receptor and calcium-sensing receptor signaling by L-histidine. Leech, C.A., Habener, J.F. Endocrinology (2003) [Pubmed]
  5. Extracellular polyamines regulate fluid secretion in rat colonic crypts via the extracellular calcium-sensing receptor. Cheng, S.X., Geibel, J.P., Hebert, S.C. Gastroenterology (2004) [Pubmed]
  6. Calcium sensing receptor: molecular cloning in rat and localization to nerve terminals. Ruat, M., Molliver, M.E., Snowman, A.M., Snyder, S.H. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  7. Molecular cloning and characterization of a rat sensory nerve Ca2+-sensing receptor. Wang, Y., Awumey, E.K., Chatterjee, P.K., Somasundaram, C., Bian, K., Rogers, K.V., Dunn, C., Bukoski, R.D. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  8. Thyroid transcription factor 1 is calcium modulated and coordinately regulates genes involved in calcium homeostasis in C cells. Suzuki, K., Lavaroni, S., Mori, A., Okajima, F., Kimura, S., Katoh, R., Kawaoi, A., Kohn, L.D. Mol. Cell. Biol. (1998) [Pubmed]
  9. Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane. Bouschet, T., Martin, S., Henley, J.M. J. Cell. Sci. (2005) [Pubmed]
  10. pH dependence of extracellular calcium sensing receptor activity determined by a novel technique. Doroszewicz, J., Waldegger, P., Jeck, N., Seyberth, H., Waldegger, S. Kidney Int. (2005) [Pubmed]
  11. Developmental and adult expression of rat calcium-sensing receptor transcripts in neurons and oligodendrocytes. Ferry, S., Traiffort, E., Stinnakre, J., Ruat, M. Eur. J. Neurosci. (2000) [Pubmed]
  12. Expression of calcium-sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion. Cheng, S.X., Okuda, M., Hall, A.E., Geibel, J.P., Hebert, S.C. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  13. Polyvalent cation-sensing mechanism increased Na(+)-independent Mg(2+) transport in renal epithelial cells. Ikari, A., Nakajima, K., Kawano, K., Suketa, Y. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  14. Gene profiling the effects of calcium deficiency versus 1,25-dihydroxyvitamin D induced hypercalcemia in rat kidney cortex. Bajwa, A., Horst, R.L., Beckman, M.J. Arch. Biochem. Biophys. (2005) [Pubmed]
  15. Expression of the calcium-sensing receptor in pancreatic islet B-cells. Rasschaert, J., Malaisse, W.J. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  16. Long-term response of cultured rat parathyroid glands to calcium and calcitriol: the effect of cryopreservation. Alvarez-Hernandez, D., Gonzalez-Suarez, I., Naves, M., Carrillo-Lopez, N., Fdez-Coto, T., Fernandez-Martin, J.L., Cannata-Andia, J.B. J. Nephrol. (2005) [Pubmed]
  17. Evidence in favor of a calcium-sensing receptor in arterial endothelial cells: studies with calindol and Calhex 231. Weston, A.H., Absi, M., Ward, D.T., Ohanian, J., Dodd, R.H., Dauban, P., Petrel, C., Ruat, M., Edwards, G. Circ. Res. (2005) [Pubmed]
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