Extracellular calcium is a direct effecter of VDR levels in proximal tubule epithelial cells that counter-balances effects of PTH on renal Vitamin D metabolism.
ABSTRACT In renal proximal tubules, VDR is transiently decreased by parathyroid hormone (PTH) during times of hypocalcemia and returns to normal levels with the rise in serum calcium (Ca). In this study we tested the hypothesis that elevated extracellular Ca induces VDR in a human renal proximal cell line (HK-2G) stably expressing PTH receptor type I. Exposure of HK-2G cells to increasing Ca concentration, up to 3mM, induced the expression of VDR. The increase in VDR occurred within 1h and was sustained over 24h. The increase in VDR was also dose-dependently increased using 20-100 nM gadolinium, suggesting the induction of VDR is regulated via the extracellular Ca sensing receptor (CaSR) with is naturally expressed in HK-2G cells. In conclusion, an extracellular Ca concentration in the physiological range is capable of direct increase of renal proximal VDR expression, and the induction mechanism represents a strategy the body may use to counterbalance effects of PTH on renal Vitamin D metabolism.
SourceAvailable from: Eleanor D Lederer
Article: Regulation of Serum Phosphate[Show abstract] [Hide abstract]
ABSTRACT: The regulation of serum phosphate, an acknowledged risk factor for chronic kidney disease and cardiovascular mortality, is poorly understood. The discovery of fibroblast growth factor 23 (FGF23) as a key regulator of renal phosphate handling and activation of vitamin D has revolutionized our comprehension of phosphate homeostasis. Through as yet undetermined mechanisms, circulating and dietary phosphate appear to have a direct effect on FGF23 release by bone cells that, in turn, causes renal phosphate excretion and decreases intestinal phosphate absorption through a decrease in vitamin D production. Thus, the two major phosphaturic hormones, PTH and FGF23, have opposing effects on vitamin D production, placing vitamin D at the nexus of phosphate homeostasis. While our understanding of phosphate homeostasis has advanced, the factors determining regulation of serum phosphate level remain enigmatic. Diet, time of day, season, gender, age, and genetics have all been identified as significant contributors to serum phosphate level. The effects of these factors on serum phosphate has major implications for what is understood as “normal” and for studies of phosphate homeostasis and metabolism. Moreover, other hormonal mediators such as dopamine, insulin-like growth factor, and angiotensin II also affect renal handling of phosphate. How the major hormone effects on phosphate handling are regulated and how the effect of these other factors are integrated to yield the measurable serum phosphate are only now beginning to be studied.This article is protected by copyright. All rights reservedThe Journal of Physiology 06/2014; 592(18). DOI:10.1113/jphysiol.2014.273979 · 4.54 Impact Factor
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ABSTRACT: The calcium sensing receptor (CaSR) has played an important role as a target in the treatment of a variety of disease states over the last 20 plus years. In this review, we give an overview of the receptor at the cellular level and then provide details as to how this receptor has been targeted to modulate cellular ion transport mechanisms. As a member of the G protein-coupled receptors family, it has a high degree of homology with a variety of other members in this class, which could explain why this receptor has been identified in so many different tissues throughout the body. This diversity of locations throughout the body sets it apart from other members of the family, and may explain how the receptor interacts with so many different organ systems in the body to modulate the physiology and pathophysiology. The receptor is unique in that it has two large exofacial lobes that sit in the extracellular environment and sense changes in a wide variety of environmental cues including: salinity, pH, amino acids concentration, polyamines to name just a few. It is for this reason that there has been a great deal of research associated with normal receptor physiology over the last 20 years. With the ongoing research in more recent years a focus on the pathophysiology has emerged and the effects of receptor mutations on cellular and organ physiology. We hope that this review will enhance and update the knowledge about the importance of this receptor and stimulate future potential investigations focused around this receptor in cellular, organ, and systemic physiology and pathophysiology.AJP Cell Physiology 05/2014; 307(3). DOI:10.1152/ajpcell.00139.2014 · 3.67 Impact Factor
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ABSTRACT: Abstract Background: Calcium-sensing receptor gene (CaSR) might be a strong component of the complex genetic background regulating calcium excretion and stone formation in kidney. The polymorphisms in different parts of the gene could be associated with calcium stone formation. Objective: The individual studies indicate a correlation between CaSR gene polymorphisms and urolithiasis but not sufficient to draw a precise result. We aimed to search literature to come to a reliable conclusion through a systematic review. Materials and methods: We have serached individiual studies regarding the issue and high quality reviews. We assessed all the studies to draw a conclusion. Conclusion: The genetic background of the neprolithiasis is an interesting issue deserving to be disscussed on. Regading genes of which, CaSR gene polymorphisms is the leading one, are studied in many individual studies but they are not sufficient to have a precise conclusion. Well-oriented and documented, phenotypically homogenous large cohort studies are needed for further evaluation.Renal Failure 07/2014; 36(8):1-6. DOI:10.3109/0886022X.2014.937673 · 0.78 Impact Factor