Expression of PTHrP, PTH/PTHrP receptor, and Ca(2+)-sensing receptor mRNAs along the rat nephron

Abstract

To provide a frame of reference for studies of renal divalent cation and phosphate metabolism, we assessed the cellular localization of kidney calcium receptor (RaKCaR), parathyroid hormone-related protein (PTHrP), and parathyroid hormone/ parathyroid hormone-related protein (PTH/PTHrP) receptor mRNA. The studies used using reverse transcription-polymerase chain reaction (RT-PCR) applied to cDNA prepared from dissected rat nephron segments and from primary cultures of mouse juxtaglomerular granular cells. With species-specific primers, PCR products of expected size were obtained for RaKCaR (967 bp), PTHrP (420 bp), and PTH/PTHrP receptor (817 bp), with product identity being confirmed by restriction digestion. RaKCaR mRNA was found in medullary and cortical thick ascending limbs (MTAL and CTAL, respectively), the macula densa-containing segment, distal convoluted tubules (DCT), and, to a lesser extent, in cortical collecting ducts (CCD). It was not found in glomeruli, proximal convoluted and straight tubules (PCT and PST, respectively), outer and inner medullary collecting ducts (OMCD and IMCD, respectively), or in juxtaglomerular granular cell isolates. PTHrP mRNA was predominantly expressed in glomeruli and at lower levels in PCT and the macula densacontaining segment but was not detectable in CTAL, MTAL, DCT, and CD segments. Presence of PTH/PTHrP receptor mRNA was demonstrated in glomeruli, PCT, PST, CTAL, MTAL, and DCT but not in CD segments. These results suggest that the function of TAL and DCT cells, in addition to being affected by PTH, may be directly altered by extracellular divalent cations through RaKCaR and that PTHrP may act in the glomerulus and proximal tubule as an autocrine or paracrine regulator of hemodynamics and phosphate transport.

Age-dependent alterations in Ca2+homeostasis: role of TRPV5 and TRPV6

“…Hyperphosphatemia leads to parathyroid cell proliferation (33), which could result in the observed hyperpara- thyroidism in 52-wk-old TRPV5 Ϫ/Ϫ mice, thereby reducing the serum phosphorus levels back to normal. Furthermore, PTH, in addition to 1,25(OH) 2 D 3 , is involved in renal and intestinal Ca 2ϩ reabsorption (1,39,51). Recent findings by our group show that PTH stimulates the expression of renal TRPV5, calbindin-D 28K , and NCX1 (47).…”

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

“…Using immunohistochemistry and molecular techniques, the PTH/PTHrp receptor has been demonstrated in the kidney of uninephrectomized rats after a protein overload (34). The PTH/PTHrp receptor is particularly found in the glomerulus and in podocytes (35)(36)(37)(38). Micropuncture studies in the rat showed that both PTH and cAMP cause a reduction in the glomerular ultrafiltration coefficient (Kf) (39).…”

Localization of Calcitonin Receptor mRNA in Rat Kidney: an In Situ Hybridization Study

“…As there is no adenylate cyclase activity in the proximal tubule, it is conjectured that the signal transduction is not likely to be mediated by cAMP [12,30]. In the proximal tubule, the presence of parathyroid hormone (PTH) receptor mRNA has been demonstrated [19,29], suggesting that the expression of both CTR and PTH receptor in the proximal tubule might play an important role in calcium homeostasis. According to Firsov et al, quantitative RT-PCR analysis after laser capture microdissection (LCM) analysis showed no expression of CTR in the proximal straight tubule [9].…”