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The calcium-sensing receptor promotes urinary acidification to prevent nephrolithiasis

dr.qinan 添加于 2009-11-1 12:01 | 757 次阅读 | 0 个评论

作者
Renkema KY, Velic A, Dijkman HB, Verkaart S, van der Kemp AW, Nowik M, Timmermans K, Doucet A, Wagner CA, Bindels RJ, Hoenderop JG
摘要
Hypercalciuria increases the risk for urolithiasis, but renal adaptive mechanisms reduce this risk. For example, transient receptor potential vanilloid 5 knockout (TPRV5(-/-)) mice lack kidney stones despite urinary calcium (Ca(2+)) wasting and hyperphosphaturia, perhaps as a result of their significant polyuria and urinary acidification. Here, we investigated the mechanisms linking hypercalciuria with these adaptive mechanisms. Exposure of dissected mouse outer medullary collecting ducts to high (5.0 mM) extracellular Ca(2+) stimulated H(+)-ATPase activity. In TRPV5(-/-) mice, activation of the renal Ca(2+)-sensing receptor promoted H(+)-ATPase-mediated H(+) excretion and downregulation of aquaporin 2, leading to urinary acidification and polyuria, respectively. Gene ablation of the collecting duct-specific B1 subunit of H(+)-ATPase in TRPV5(-/-) mice abolished the enhanced urinary acidification, which resulted in severe tubular precipitations of Ca(2+)-phosphate in the renal medulla. In conclusion, activation of Ca(2+)-sensing receptor by increased luminal Ca(2+) leads to urinary acidification and polyuria. These beneficial adaptations facilitate the excretion of large amounts of soluble Ca(2+), which is crucial to prevent the formation of kidney stones.
详细资料
- 关键词: Animals; Aquaporin 2/metabolism; Calcium/urine; Calcium Channels/genetics; Hydrogen-Ion Concentration; Hypercalciuria/*urine; Intestines/metabolism; Kidney/metabolism; Kidney Tubules, Collecting/enzymology; Mice; Mice, Knockout; Nephrolithiasis/*urine; Phenotype; Phosphate Transport Proteins/metabolism; Receptors, Calcium-Sensing/*metabolism; TRPV Cation Channels/genetics; Vacuolar Proton-Translocating ATPases/genetics/*metabolism
- 文献种类: Journal Article
- 期刊名称: Journal of the American Society of Nephrology : JASN
- 期刊缩写: J Am Soc Nephrol
- 期卷页: 2009年第20卷第8期 1705-1713页
- 地址: Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
- ISBN: 1533-3450
- 备注:PMID:19470676
学科领域生物医药 » 临床医学
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