Localization of the extracellular Ca²⁺/polyvalent cation-sensing protein in rat kidney

Abstract

We previously identified transcripts encoding a G protein-coupled, extracellular calcium/polyvalent cation-sensing receptor, RaKCaR, in rat kidney (D. Riccardi, J. Park, W.-S. Lee, G. Gamba, E. M. Brown, and S. C. Hebert. Proc. Natl. Acad. Sci. USA 92: 131–135, 1994), which was proposed to provide the mechanism for modulating a variety of renal functions in response to changes in extracellular Ca2+ (E. M. Brown. In: Handbook of Physiology. Bethesda, MD: Am. Physiol. Soc., 1992, sect. 8, vol. 2, chapt. 39, p. 1841–1916; and S. C. Hebert. Kidney Int. 50: 2129–2139, 1996). Here, we examine the cellular and regional distribution of receptor protein by immunofluorescence microscopy using a polyclonal antibody raised against a 22 amino acid region of the NH2 terminus of the receptor. The most intense fluorescence was seen at the basolateral border of cortical thick ascending limb cells. Basolateral staining for the receptor was also detected in medullary thick ascending limbs, in macula densa cells identified by costaining with antibody to brain nitric oxide synthase, NOS-B1, and in distal convoluted tubule cells distinguished by costaining for the apical thiazide-sensitive Na+-Cl−cotransporter. Apical anti-RaKCaR staining was detected at the base of the brush border of proximal tubules with decreasing intensity from S1 to S3 segments. In cortical collecting ducts, anti-RaKCaR staining was detected in some, but not all, type A intercalated cells identified by costaining with anti-H+-ATPase and anti-AE1 Cl−/[Formula: see text]exchanger antibodies. The present study demonstrates that RaKCaR protein is expressed in many different nephron segments and that the polarity of receptor expression varies with cell type along the nephron. These results suggest potential roles for the extracellular Ca2+/polyvalent cation-sensing receptor in responding to both circulating and urinary concentrations of divalent minerals and potentially other polyvalent cations (e.g., aminoglycoside antibiotics) to modulate nephron function.

Beneficial Effects of Calcimimetics on Progression of Renal Failure and Cardiovascular Risk Factors

“…We cannot exclude that the lower SBP in our animals played a role in attenuating progression of renal failure, but such near normalization of BP had not been observed in a previous study (9) suggesting that the significant effect of low PTH is at least not fully explained by differences in BP. The calcium sensing receptor is expressed by various types of renal cells (45)(46)(47), but similar changes were seen in R-568 treated and PTX animals; it is therefore unlikely that a direct action of R-568 on the calcium sensing receptor played a role in the beneficial effect on progression observed in the present study. It is noteworthy that we observed no effects of R-568 or 5% dietary calcium supplement on BP in rats with normal renal function (unpublished data).…”

Association of Paracellin-1 with ZO-1 Augments the Reabsorption of Divalent Cations in Renal Epithelial Cells

“…In addition, the elevation of divalent cations in the basal compartment may inhibit calcium transport via PCLN-1. The extracellular calcium/polyvalent cation-sensing protein is expressed in the basal membrane of epithelial cells in the proximal tubule, TAL, and distal tubule (28). It has been reported that the elevation of either basal calcium or magnesium decreases the reabsorption of calcium and magnesium in TAL (29).…”

Drug-induced acid-base disorders

“…Under physiological conditions, the increased serum Ca 2+ levels stimulate this receptor and decrease the active reabsorption of Na + . This reduces the luminal positive driving force and results in increased urinary Ca excretion [171]. Activation of the CaSR can disrupt electrolyte transport via inhibition of four different pathways: (1) renal channel proteins, such as the Na-K-2Cl cotransporter (NKCC2), (2) ROMK, (3) Na + /K + -ATPase, and (4) paracellular diffusion [146].…”