AJP - Renal Physiology, Vol 271, Issue 3 736-F743, Copyright © 1996 by American Physiological Society

ARTICLES

Ontogeny of the extracellular calcium-sensing receptor in rat kidney

N. Chattopadhyay, M. Baum, M. Bai, D. Riccardi, S. C. Hebert, H. W. Harris and E. M. Brown
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

We recently cloned extracellular Ca(2+)-sensing receptors (CaRs) from bovine parathyroid and rat kidney that play key roles in Ca2+ homeostasis. Inactivating mutations of the CaR in the inherited human disorder, familial hypocalciuric hypercalcemia, cause reduced responsiveness of the parathyroid to extracellular Ca2+ (Cao2+), as well as abnormally avid renal tubular reabsorption of both Ca2+ and Mg2+ in the distal tubule, suggesting an important role for the CaR in regulating parathyroid hormone (PTH) secretion and renal handling of divalent cations. High Cao2+ also inhibits vasopressinstimulated adenosine 3',5'-cyclic monophosphate accumulation in the medullary thick ascending limb (MTAL) and water reabsorption in the collecting duct (CD) and modulates various other aspects of renal function. The relevance of the CaR to these processes, however, is uncertain. Reduced responsiveness of vasopressin-and PTH-mediated actions on the kidney have been described in the newborn that could potentially reflect effects of the CaR on these aspects of renal function. To define further the role of the CaR in regulating renal function, including the above-mentioned changes during the perinatal period, therefore, we have studied its ontogeny in rat kidney. Northern and Western blot analyses, as well as immunohistochemistry with CaR-specific probes, demonstrate that there is little prenatal expression of the extracellular Ca(2+)-sensing receptor, except in large tubules and branching ureteric buds of developing nephrons. Postnatally, CaR mRNA and protein increase markedly during the 1st wk, related principally to expression of the receptor in the developing TAL and, to a lesser extent, in the CD. The level of expression of the receptor remains nearly constant after postnatal day 14. These results demonstrate that the perinatal increases in expression of CaR mRNA and protein parallel its tissue-specific renal expression. Furthermore, it is possible that some of the previously described changes in renal handling of divalent cations and water in the perinatal and immediate postnatal period are related, in part, to the increasing levels of expression of the CaR and resultant inhibitory effects on the actions of PTH and antidiuretic hormone on the developing nephron.

This article has been cited by other articles:

				H. I. Abdullah, P. L. Pedraza, J. C. McGiff, and N. R. Ferreri Calcium-sensing receptor signaling pathways in medullary thick ascending limb cells mediate COX-2-derived PGE2 production: functional significance Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1082 - F1089. [Abstract] [Full Text] [PDF]

				H. I. Abdullah, P. L. Pedraza, J. C. McGiff, and N. R. Ferreri CaR activation increases TNF production by mTAL cells via a Gi-dependent mechanism Am J Physiol Renal Physiol, February 1, 2008; 294(2): F345 - F354. [Abstract] [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]

				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]

				D. T. Ward, E. M. Brown, and H. W. Harris Disulfide Bonds in the Extracellular Calcium-Polyvalent Cation-sensing Receptor Correlate with Dimer Formation and Its Response to Divalent Cations in Vitro J. Biol. Chem., June 5, 1998; 273(23): 14476 - 14483. [Abstract] [Full Text] [PDF]

				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]

				D. Riccardi, A. E. Hall, N. Chattopadhyay, J. Z. Xu, E. M. Brown, and S. C. Hebert Localization of the extracellular Ca2+/polyvalent cation-sensing protein in rat kidney Am J Physiol Renal Physiol, March 1, 1998; 274(3): F611 - F622. [Abstract] [Full Text] [PDF]

				N. Chattopadhyay, I. Cheng, K. Rogers, D. Riccardi, A. Hall, R. Diaz, S. C. Hebert, D. I. Soybel, and E. M. Brown Identification and localization of extracellular Ca2+-sensing receptor in rat intestine Am J Physiol Gastrointest Liver Physiol, January 1, 1998; 274(1): G122 - G130. [Abstract] [Full Text] [PDF]