References

porozendo

Остеопороз и остеопатии

Osteoporosis and Bone Diseases

2072-26802311-0716

Endocrinology Research Centre

10.14341/osteo2010332-36

porozendo-4194

Research Article

Статьи

Articles

РОЛЬ КАЛЬЦИЙ-ЧУВСТВИТЕЛЬНОГО РЕЦЕПТОРА В ПОДДЕРЖАНИИ СИСТЕМЫ КАЛЬЦИЕВОГО ГОМЕОСТАЗА

ROL' KAL'TsIY-ChUVSTVITEL'NOGO RETsEPTORA V PODDERZhANII SISTEMY KAL'TsIEVOGO GOMEOSTAZA

Mirnaya

S S

Pigarova

E A

Belyaeva

A V

Mokrysheva

N G

Tyul'pakov

A N

Rozhinskaya

L Ya

2010

15122010

133

№3 (2010)

3236

2010

Mirnaya S.S., Pigarova E.A., Belyaeva A.V., Mokrysheva N.G., Tyul'pakov A.N., Rozhinskaya L.Y.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.osteo-endojournals.ru/jour/article/view/4194

Кальций-чувствительный рецептор (КЧР), относящийся к семейству рецепторов, сопряженных с G-белком, имеет большое значение для метаболических процессов, играя ключевую роль в регуляции кальциевого гомеостаза. Он широко экспрессируется в различных тканях организма, обеспечивая постоянную концентрацию ионизированного кальция в плазме. В дополнение к своей основной роли, он регулирует важные клеточные функции, такие как защиту от апоп- тоза и клеточную пролиферацию. КЧР является мишенью для различных медикаментов, разработанных для модифи- кации функции околощитовидных желез и терапии метаболических остеопатий. Активирующие и инактивирующие мутации в гене КЧР вызывают изменения гомеостаза кальция. Помимо мутаций, приводящих к выраженным наруше- ниям функции рецептора и ассоциированных с патологическими состояниями, известен ряд полиморфных вариантов гена КЧР, встречающихся у здоровых людей.

Calcium-sensing receptor (CaSR), a member of G proteincoupled receptors family, plays a key role in systemic calcium homeostasis regulation. It is expressed in a variety of tissues, and is responsible for maintaining plasma calcium concentration. In addition, the CaSR is known to regulate some important cellular processes such as apoptosis and proliferation. CaSR is a drug target for calcimimetics and calcilytics, agents used for modification of parathyroid cells function and treatment of some pathologic conditions. Inactivating or activating mutations of the CaSR gene cause different disorders of calcium metabolism. Polymorphic variants of the gene have been described in healthy populations.

кальциевый гомеостазкальций-чувствительный рецепторкальцимиметики

References1

Дедов И.И., Мельниченко Г.А., Фадеев В.В. Эндокри- нология.- М., 2000.

Alpern R J., Hebert S C., Seldin and Giebisch's The Kidney (Fourth Edition) Physiology and Pathophysiology. 2008. Elsevier Inc.

Bai M, Quinn S, Trivedi S, et al. Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor. J Biol Chem. 1996; 271(32):19537-45.

Charrié A, Chikh K, Peix JL, et al. Calcium-sensing receptor autoantibodies in primary hyperparathyroidism. Clin Chim Acta. 2009;406(1-2):94-7.

Chattopadhyay N. Biochemistry, physiology and pathophysiology of the extracellular calcium-sensing receptor. Int J Biochem Cell Biol. 2000;32(8):789-804.

Chattopadhyay N. Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy. Am J Physiol Endocrinol Metab - 2006 - 290 - pp.761-770.

Corbetta S, Eller-Vainicher C, Filopanti M, et al. R990G polymorphism of the calcium-sensing receptor and renal calcium excretion in patients with primary hyperparathyroidism. European Journal of Endocrinology (2006), 155, 687-692.

D'Souza-Li L. The calcium-sensing receptor and related diseases. Arq Bras Endocrinol Metabol (2006) 50: 628-639.

Dvorak MM, Siddiqua A, Ward DT, Carter DH, Dallas SL, Nemeth EF, Riccardi D. Proc Natl Acad Sci USA. 2004;101(14):5140-5145.

Fray JC, Lush DJ, Park CS. Interrelationship of blood flow, juxtaglomerular cells, and hypertension: role of physical equilibrium and Ca. Am J Physiol. 1986;251 (4 Pt 2):R643-62.

Goodman WG. Calcium-sensing receptors. Semin Nephrol. 2004 Jan;24(1):17-24.

Gowen M, Stroup GB, Dodds RA, et all. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest. 2000;105(11):1595-1604.

Hendy GN, D'Souza-Li L, Yang B, Canaff L, Cole DE. Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat. 2000;16(4):281-96.

Houillier P, Paillard M. Calcium-sensing receptor and renal cation handling. Nephrol Dial Transplant. 2003;18(12):2467-70.

Hu J, McLarnon SJ, Mora S, Jiang J, et al. A region in the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+. J Biol Chem. 2005;280(6):5113-20.

Huan J, Martuseviciene G, Olgaard K, Lewin E. Eur J Clin Invest. Calcium-sensing receptor and recovery from hypocalcaemia in thyroparathyroidectomized rats. 2007 - 37(3) - pp. 214-221.

Kantham L, Quinn SJ, Egbuna OI et all. The calciumsensing receptor (CaSR) defends against hypercalcemia independently of its regulation of parathyroid hormone secretion. Am J Physiol Endocrinol Metab - 2009;297(4) - pp. 915-23.

Kapur K, Johnson T, Beckmann ND, et all. Genome- Wide Meta-Analysis for Serum Calcium Identifies Significantly Associated SNPs near the Calcium-Sensing Receptor (CASR) Gene. PLoS Genet. - 2010 July - 6(7) - e1001035 - рр.1-12.

Kifor O, McElduff A, LeBoff MS, et all. Activating antibodies to the calcium-sensing receptor in two patients with autoimmune hypoparathyroidism. J Clin Endocrinol Metab. 2004;89(2):548-556.

Kobilka B. Allosteric activation of the CaR by L-amino acids. Proc Natl Acad Sci U S A, 2000 vol.97, 9, 4419-4420.

Kos CH, Karaplis AC, Peng JB et all. The calcium-sensing receptor is required for normal calcium homeostasis independent of parathyroid hormone. J Clin Invest. - 2003;111(7) - pp.1021-8.

Kovacs CS. Calcium and bone metabolism during pregnancy and lactation. J Mammary Gland Biol Neoplasia 10: 105-118, 2005.

Lerolle N, Coulet F, Lantz B et al. No evidence for point mutations of the calcium-sensing receptor in familial idiopathic hypercalciuria. Nephrol Dial Transplant 2001; 16: 2317-2322.

Levi R, Ben-Dov IZ, Lavi-Moshayoff V, et al. Increased parathyroid hormone gene expression in secondary hyperparathyroidism of experimental uremia is reversed by calcimimetics: correlation with posttranslational modification of the trans acting factor AUF1. J Am Soc Nephrol. 2006;17(1):107-12.

Lewin E, Wang W, Olgaard K. Nephrol Dial Transplant. Rapid recovery of plasma ionized calcium after acute induction of hypocalcaemia in parathyroidectomized and nephrectomized rats. 1999;14(3):604-609.

Lienhardt A, Bai M, Lagarde JP, et al. Activating mutations of the calcium-sensing receptor: management of hypocalcemia. J Clin Endocrinol Metab. 2001;86(11):5313-23.

Miedlich S, Lamesch P, Mueller A, Paschke R. Frequency of the calcium-sensing receptor variant A986S in patients with primary hyperparathyroidism. Eur J Endocrinol. 2001;145:421-427.

Nemeth EF. The search for calcium receptor antagonists (calcilytics). J Mol Endocrinol. 2002;29(1):15-21.

Obermannova B., Banghova K., Sumník Z., et al. Unusually severe phenotype of neonatal primary hyperparathyroidism due to a heterozygous inactivating mutation in the CASR gene Eur J Pediatr. 2009; 168(5):569-73. 3 Pallais JC, Kifor O, Chen YB, Slovik D, Brown EM. Acquired hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor. N Engl J Med. 2004;351(4):362-369.

Peacock M, Bilezikian JP, Klassen PS, Guo MD, Turner SA, Shoback D. Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2005;90(1):135-141.

Petrel C, Kessler A, Dauban P, Dodd RH, Rognan D, Ruat M. Positive and negative allosteric modulators of the Ca2+- sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain. J Biol Chem. 2004; 279(18):18990-7.

Petrucci M, Scott P, Ouimet D et al. Evaluation of the calcium-sensing receptor gene in idiopathic hypercalciuria and calcium nephrolithiasis. Kidney Int 2000; 58: 38-42.

Quinn SJ, Bai M, Brown EM. pH Sensing by the calciumsensing receptor. J Biol Chem. 2004, 279(36):37241-9.

Quinn SJ, Kifor O, Trivedi S, Diaz R, Vassilev P, Brown E. Sodium and ionic strength sensing by the calcium receptor. J Biol Chem. 1998 Jul 31;273(31):19579-86.

Radu Mihai The calcium sensing receptor: from understanding parathyroid calcium homeostasis to bone metastases Ann R Coll Surg Engl 2008; 90: 271-277.

Schwartz TW, Holst B. Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors. J Recept Signal Transduct Res. 2006;26(1-2):107-28.

Scillitani A, Guarnieri V, Battista C, et al. Primary Hyperparathyroidism and the Presence of Kidney Stones Are Associated with Different Haplotypes of the Calcium-Sensing Receptor J Clin Endocrinol Metab, 2007, 92(1):277-283

Takeyama S, Yoshimura Y, Shirai Y, et all. Low calcium environment effects osteoprotegerin ligand/osteoclast differentiation factor. Biochem Biophys Res Commun. 2000;276(2):524-529.

Tfelt-Hansen J, Brown EM. The calcium-sensing receptor in normal physiology and pathophysiology: a review. Crit Rev Clin Lab Sci. 2005;42(1):35-70.

Thakker RV. Diseases associated with the extracellular calcium-sensing receptor. Cell Calcium. 2004 Mar;35(3):275-82. Theman TA, Collins MT. The Role of the Calcium-Sensing Receptor in Bone Biology and Pathophysiology. Curr Pharm Biotechnol. 2009 April; 10(3): 289-301.

Valimaki S, Farnebo F, Forsberg L, Larsson C, Farnebo

LO. Heterogeneous expression of receptor mRNAs in parathyroid glands of secondary hyperparathyroidism. Kidney Int. 2001 Nov;60(5):1666-75.

Vanhouten J, Dann P, McGeoch G, et all. The calciumsensing receptor regulates mammary gland parathyroid hormonerelated protein production and calcium transport. J Clin Invest 113: 598-608, 2004.

Vezzoli G, Tanini A, Ferrucci L, et al. Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients. J Am Soc Nephrol. 2002; 13(10):2517-23.

Vezzoli G, Terranegra A, Arcidiacono T, et all. Calcium kidney stones are associated with a haplotype of the calciumsensing receptor gene regulatory region. Nephrol Dial Transplant. - 2010;25(7) - pp. 2245-52.

Wang NN, Wang XY, Peng T, et al. Expression of the calcium receptor CaR in the parathyroid of secondary hyperparathyroidism patients. Chin Med J (Engl). 2004;117(9):1408-10.

Watanabe H, Sutton RA. Renal calcium handling in familial hypocalciuric hypercalcemia. Kidney Int. 1983;24(3):353-7.

Yamauchi M, Sugimoto T, Yamaguchi T, Yano S, Kanzawa M, et al. Association of polymorphic alleles of the calciumsensing receptor gene with the clinical severity of primary hyperparathyroidism. Clin Endocrinol (Oxf) 2001;55:373-379.

Yano S, Sugimoto T, Tsukamoto T, Chihara K, Kobayashi A, Kitazawa S, Maeda S, Kitazawa R. Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism. Kidney Int. 2000;58(5):198

The authors declare that there are no conflicts of interest present.