scholarly journals Calcium-Sensing Receptor Expression and Parathyroid Hormone Secretion in Hyperplastic Parathyroid Glands from Humans

2005 ◽  
Vol 16 (7) ◽  
pp. 2190-2197 ◽  
Author(s):  
Sagrario Cañadillas ◽  
Antonio Canalejo ◽  
Rafael Santamaría ◽  
Maria E. Rodríguez ◽  
Jose C. Estepa ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Secretion ◽  
Receptor Expression ◽  
Parathyroid Glands ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

scholarly journals Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism

2005 ◽  
Vol 153 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Takehisa Kawata ◽  
Yasuo Imanishi ◽  
Keisuke Kobayashi ◽  
Takao Kenko ◽  
Michihito Wada ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Secondary Hyperparathyroidism ◽  
Murine Model ◽  
Hormone Secretion ◽  
Suppressive Effect ◽  
Receptor Expression ◽  
Parathyroid Glands ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet’s effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1 transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93–99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.

Association of Polymorphic Alleles of the Calcium-Sensing Receptor Gene with Parathyroid Hormone Secretion in Hemodialysis Patients

Nephron ◽  
2000 ◽  
Vol 85 (4) ◽  
pp. 317-323 ◽  
Author(s):  
Shozo Yano ◽  
Toshitsugu Sugimoto ◽  
Michiko Kanzawa ◽  
Tatsuo Tsukamoto ◽  
Tetsuya Hattori ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Receptor Gene ◽  
Hormone Secretion ◽  
Hemodialysis Patients ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Calcium Sensing Receptor Gene

scholarly journals A Novel Calcium-Sensing Receptor Antagonist Transiently Stimulates Parathyroid Hormone Secretion in Vivo

Endocrinology ◽  
2005 ◽  
Vol 146 (4) ◽  
pp. 2015-2022 ◽  
Author(s):  
Brian J. Arey ◽  
Ramakrishna Seethala ◽  
Zhengping Ma ◽  
Aberra Fura ◽  
Jennifer Morin ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Receptor Antagonist ◽  
Hormone Secretion ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

scholarly journals Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Patricia P. Centeno ◽  
Amanda Herberger ◽  
Hee-Chang Mun ◽  
Chialing Tu ◽  
Edward F. Nemeth ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Secretion ◽  
Phosphate Concentration ◽  
Wild Type ◽  
Calcium Sensing Receptor ◽  
Mediated Action ◽  
Calcium Sensing ◽  
Competitive Antagonism ◽  
Phosphate Sensing ◽  
Phosphate Sensor

Abstract Extracellular phosphate regulates its own renal excretion by eliciting concentration-dependent secretion of parathyroid hormone (PTH). However, the phosphate-sensing mechanism remains unknown and requires elucidation for understanding the aetiology of secondary hyperparathyroidism in chronic kidney disease (CKD). The calcium-sensing receptor (CaSR) is the main controller of PTH secretion and here we show that raising phosphate concentration within the pathophysiologic range for CKD significantly inhibits CaSR activity via non-competitive antagonism. Mutation of residue R62 in anion binding site-1 abolishes phosphate-induced inhibition of CaSR. Further, pathophysiologic phosphate concentrations elicit rapid and reversible increases in PTH secretion from freshly-isolated human parathyroid cells consistent with a receptor-mediated action. The same effect is seen in wild-type murine parathyroid glands, but not in CaSR knockout glands. By sensing moderate changes in extracellular phosphate concentration, the CaSR represents a phosphate sensor in the parathyroid gland, explaining the stimulatory effect of phosphate on PTH secretion.

scholarly journals Effect of aluminium on calcium-sensing receptor expression, proliferation, and apoptosis of parathyroid glands from rats with chronic renal failure

2003 ◽  
Vol 63 ◽  
pp. S39-S43 ◽  
Author(s):  
Ignacio González-Suárez ◽  
Manuel Naves ◽  
Carmen Díaz-Corte ◽  
José L. Fernández-Martín ◽  
Primitiva Menéndez-Rodríguez ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Receptor Expression ◽  
Parathyroid Glands ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Proliferation And Apoptosis
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