|
| |
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Journal of Experimental Biology, Vol 200, Issue 2 295-302, Copyright © 1997 by Company of Biologists
JOURNAL ARTICLES |
SC Hebert, EM Brown and HW Harris
Renal Division, Brigham and Women's Hospital, Boston, MA 02115, USA. shebert@bustoff.bwh.harvard.edu
The divalent mineral cations Ca2+ and Mg2+ play many and diverse roles both in the function of cells and in extracellular processes. The metabolism of these cations is a complex process involving the coordinated function of several organ systems and endocrine glands. A recently cloned G-protein-coupled receptor responds to extracellular calcium concentration (Ca2+0-sensing receptor, CaSR) and mediates several of the known effects of Ca2+0 on parathyroid and renal function. The CaSR, which is also expressed in a number of other tissues including thyroidal C-cells, brain and gastrointestinal tract, may function as a Ca2+0 sensor in these tissues as well. Thus, Ca2+0 is a first messenger (or hormone) which, via CaSR-mediated activation of second messenger systems (e.g. phospholipases C and A2, cyclic AMP) leads to altered function of these cells. Several mutations in the human CaSR gene have been identified and shown to cause three inherited diseases of calcium homeostasis, clearly implicating the CaSR as an important component of the homeostatic mechanism for divalent mineral ions. Ca2+ and Mg2+ losses from the body are regulated by altering the urinary excretion of these divalent cations. The localization of the CaSR transcripts and protein in the kidney not only provides a basis for a direct Ca2+0 (or Mg2+0)-mediated regulation of Ca2+ (and Mg2+) excretion but also suggests a functional link between divalent mineral and water metabolism. In the kidney, the thick ascending limb of Henle (TAL) plays crucial roles in regulating both divalent mineral reabsorption and urine concentration. Recent studies have suggested models whereby extracellular Ca2+, via the CaSR expressed in the TAL as well as in the collecting duct system, modulates both Ca2+ 0 and Mg2+ 0 as well as water reabsorbtion. When taken together, these studies suggest that the CaSR not only provides the primary mechanism for Ca2+ 0-mediated regulation of parathyroid hormone secretion from parathyroid glands but also for direct modulation of renal divalent mineral excretion and urinary concentrating ability. These latter functions may furnish a mechanism for integrating and balancing water and divalent cation losses that minimizes the risk of urinary tract stone formation. This mechanism can explain hypercalcemia-mediated polyuria (diabetes insipidus).
This article has been cited by other articles:
|
|
 |
|
  O. Rey, S. H. Young, R. Papazyan, M. S. Shapiro, and E. Rozengurt Requirement of the TRPC1 Cation Channel in the Generation of Transient Ca2+ Oscillations by the Calcium-sensing Receptor J. Biol. Chem., December 15, 2006; 281(50): 38730 - 38737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Valenti, G. Procino, G. Tamma, M. Carmosino, and M. Svelto Minireview: Aquaporin 2 Trafficking Endocrinology, December 1, 2005; 146(12): 5063 - 5070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Y. Renkema, T. Nijenhuis, B. C.J. van der Eerden, A. W.C.M. van der Kemp, H. Weinans, J. P.T.M. van Leeuwen, R. J.M. Bindels, and J. G.J. Hoenderop Hypervitaminosis D Mediates Compensatory Ca2+ Hyperabsorption in TRPV5 Knockout Mice J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3188 - 3195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Rey, S. H. Young, J. Yuan, L. Slice, and E. Rozengurt Amino Acid-stimulated Ca2+ Oscillations Produced by the Ca2+-sensing Receptor Are Mediated by a Phospholipase C/Inositol 1,4,5-Trisphosphate-independent Pathway That Requires G12, Rho, Filamin-A, and the Actin Cytoskeleton J. Biol. Chem., June 17, 2005; 280(24): 22875 - 22882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Sakwe, L. Rask, and E. Gylfe Protein Kinase C Modulates Agonist-sensitive Release of Ca2+ from Internal Stores in HEK293 Cells Overexpressing the Calcium Sensing Receptor J. Biol. Chem., February 11, 2005; 280(6): 4436 - 4441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Brown Mutant Extracellular Calcium-Sensing Receptors and Severity of Disease J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1246 - 1248. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Loretz, C. Pollina, S. Hyodo, Y. Takei, W. Chang, and D. Shoback cDNA Cloning and Functional Expression of a Ca2+-sensing Receptor with Truncated C-terminal Tail from the Mozambique Tilapia (Oreochromis mossambicus) J. Biol. Chem., December 17, 2004; 279(51): 53288 - 53297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Hough, D. Bogani, M. T. Cheeseman, J. Favor, M. A. Nesbit, R. V. Thakker, and M. F. Lyon Activating calcium-sensing receptor mutation in the mouse is associated with cataracts and ectopic calcification PNAS, September 14, 2004; 101(37): 13566 - 13571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Pallais, O. Kifor, Y.-B. Chen, D. Slovik, and E. M. Brown Acquired Hypocalciuric Hypercalcemia Due to Autoantibodies against the Calcium-Sensing Receptor N. Engl. J. Med., July 22, 2004; 351(4): 362 - 369. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hentschel, J. Nearing, H. W. Harris, M. Betka, M. Baum, S. C. Hebert, and M. Elger Localization of Mg2+-sensing shark kidney calcium receptor SKCaR in kidney of spiny dogfish, Squalus acanthias Am J Physiol Renal Physiol, September 1, 2003; 285(3): F430 - F439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kellermayer, D. P. Aiello, A. Miseta, and D. M. Bedwell Extracellular Ca2+ sensing contributes to excess Ca2+ accumulation and vacuolar fragmentation in a pmr1{Delta} mutant of S. cerevisiae J. Cell Sci., April 15, 2003; 116(8): 1637 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Frick and D. A. Bushinsky Molecular Mechanisms of Primary Hypercalciuria J. Am. Soc. Nephrol., April 1, 2003; 14(4): 1082 - 1095. [Full Text] [PDF]
|
|
|
|
|
|
O. Kifor, F. D. Moore Jr., M. Delaney, J. Garber, G. N. Hendy, R. Butters, P. Gao, T. L. Cantor, I. Kifor, E. M. Brown, et al. A Syndrome of Hypocalciuric Hypercalcemia Caused by Autoantibodies Directed at the Calcium-Sensing Receptor J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 60 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vargas-Poussou, C. Huang, P. Hulin, P. Houillier, X. Jeunemaitre, M. Paillard, G. Planelles, M. Dechaux, R. T. Miller, and C. Antignac Functional Characterization of a Calcium-Sensing Receptor Mutation in Severe Autosomal Dominant Hypocalcemia with a Bartter-Like Syndrome J. Am. Soc. Nephrol., September 1, 2002; 13(9): 2259 - 2266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Sanders, N. Chattopadhyay, O. Kifor, T. Yamaguchi, and E. M. Brown Ca2+-sensing receptor expression and PTHrP secretion in PC-3 human prostate cancer cells Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1267 - E1274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wenning, C. F. J. Erxleben, and R. L. Calabrese Indirectly Gated Cl--Dependent Cl- Channels Sense Physiological Changes of Extracellular Chloride in the Leech J Neurophysiol, October 1, 2001; 86(4): 1826 - 1838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang, S.-J. An, W.-H. Wang, J. C. McGiff, and N. R. Ferreri CaR-mediated COX-2 expression in primary cultured mTAL cells Am J Physiol Renal Physiol, October 1, 2001; 281(4): F658 - F664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Wang, T.-H. Kwon, C. Li, A. Flyvbjerg, M. A. Knepper, J. Frokiar, and S. Nielsen Altered expression of renal aquaporins and Na+ transporters in rats treated with L-type calcium blocker Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2001; 280(6): R1632 - R1641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Brown and R. J. MacLeod Extracellular Calcium Sensing and Extracellular Calcium Signaling Physiol Rev, January 1, 2001; 81(1): 239 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Handlogten, N. Shiraishi, H. Awata, C. Huang, and R. T. Miller Extracellular Ca2+-sensing receptor is a promiscuous divalent cation sensor that responds to lead Am J Physiol Renal Physiol, December 1, 2000; 279(6): F1083 - F1091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Scheinman, L. M. Guay-Woodford, R. V. Thakker, and D. G. Warnock Genetic Disorders of Renal Electrolyte Transport N. Engl. J. Med., April 15, 1999; 340(15): 1177 - 1187. [Full Text] [PDF]
|
|
|
|
|
|
G. E.-H. Fuleihan Calcium-Regulated Renal Calcium Handling in Healthy Men--Authors' Response J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1487a - 1488. [Full Text]
|
|
|
|
|
|
J. M. Sands, F. X. Flores, A. Kato, M. A. Baum, E. M. Brown, D. T. Ward, S. C. Hebert, and H. W. Harris Vasopressin-elicited water and urea permeabilities are altered in IMCD in hypercalcemic rats Am J Physiol Renal Physiol, May 1, 1998; 274(5): F978 - F985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Waldegger and T. J. Jentsch Functional and Structural Analysis of ClC-K Chloride Channels Involved in Renal Disease J. Biol. Chem., August 4, 2000; 275(32): 24527 - 24533. [Abstract] [Full Text] [PDF]
|
|
