An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation

Bone ◽  
2010 ◽  
Vol 46 (2) ◽  
pp. 534-542 ◽  
Author(s):  
Sanjay Kumar ◽  
Christopher J. Matheny ◽  
Sandra J. Hoffman ◽  
Robert W. Marquis ◽  
Maggie Schultz ◽  
...  
Keyword(s):  
Bone Formation ◽  
Receptor Antagonist ◽  
Plasma Concentrations ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Active Calcium ◽  
Orally Active

Short-acting 5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one derivatives as orally-active calcium-sensing receptor antagonists

2009 ◽  
Vol 19 (16) ◽  
pp. 4555-4559 ◽  
Author(s):  
Mary T. Didiuk ◽  
David A. Griffith ◽  
John W. Benbow ◽  
Kevin K.C. Liu ◽  
Daniel P. Walker ◽  
...  
Keyword(s):  
Calcium Sensing Receptor ◽  
Receptor Antagonists ◽  
Short Acting ◽  
Calcium Sensing ◽  
Active Calcium ◽  
Orally Active

scholarly journals The Corpuscles of Stannius, Calcium-Sensing Receptor, and Stanniocalcin: Responses to Calcimimetics and Physiological Challenges

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3002-3010 ◽  
Author(s):  
Michael P. Greenwood ◽  
Gert Flik ◽  
Graham F. Wagner ◽  
Richard J. Balment
Keyword(s):  
Mrna Expression ◽  
Broad Band ◽  
Plasma Concentrations ◽  
Immunoblot Analysis ◽  
Pcr Analysis ◽  
Endocrine Regulation ◽  
Calcium Sensing Receptor ◽  
Corpuscles Of Stannius ◽  
Calcium Sensing

This study has examined whether the calcium-sensing receptor (CaSR) plays a role in control of stanniocalcin-1 (STC-1), the dominant calcium regulatory hormone of fish, comparable with that demonstrated for CaSR in the mediation of ionized calcium regulation of PTH secretion in mammals. In a previous study, we have cloned flounder STC-1 from the corpuscles of Stannius (CS). Here, we report the cloning and characterization of the CS CaSR, and the in vivo responses of this system to altered salinity, EGTA induced hypocalcemia, and calcimimetic administration. Quantitative PCR analysis demonstrated, for the first time, that the CS are major sites of CaSR expression in flounder. Immunoblot analysis of CS proteins with CaSR-specific antibodies revealed a broad band of approximately 215–300 kDa under nonreducing conditions, and bands of approximately 215–300 kDa and approximately 120–150 kDa under reducing conditions. There were no differences in CS CaSR mRNA expression or plasma STC-1 levels between seawater and freshwater (FW)-adapted fish, although CS STC-1 mRNA expression was lower in FW animals. Immunoblots showed that glycosylated monomeric forms of the CaSR migrated at a lower molecular mass in CS samples from FW animals. The ip administration of EGTA rapidly induced hypocalcemia, and a concomitant lowering of plasma STC-1. Calcimimetic administration (1 mg/kg R-568) rapidly increased plasma STC-1 levels, and reduced plasma concentrations of calcium, phosphate, and magnesium when compared with S-568-treated controls. Together, these findings support an evolutionary conserved role for the CaSR in the endocrine regulation of calcium before the appearance of parathyroid glands in tetrapods.

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
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