Increased endothelin-1 expression in the kidney in hypercalcemic rats

Naoki Shiraishi, Kenichiro Kitamura, Yukimasa Kohda, Takefumi Narikiyo, Masataka Adachi, Taku Miyoshi, Kozo Iwashita, Hiroshi Nonoguchi, R. Tyler Miller, Kimio Tomita

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background. Although hypercalcemia causes diuresis and natriuresis, the molecular mechanisms of these effects are not well established. Recently, the important role of the calcium-sensing receptor (CaR) in hypercalcemia-induced polyuria was reported. Endothelin-1 (ET-1) that is locally produced in the nephron has been suggested to have the natriuretic and/or diuretic effects in the kidney. Therefore, we hypothesized that ET-1 expression could be increased through the activation of CaR in the kidney in hypercalcemia. Methods. Rats were made hypercalcemic by dihydrotachysterol (DHT) treatment. The urinary concentration of ET-1 and the mRNA expression of ET-1 in the kidney were determined. Immunohistochemistry was performed to determine types of the cells that produce ET-1. CaR and ET-1 promoter luciferase constructs were co-expressed in COS-7 cells and the ET-1 promoter activity following the addition of extracellular calcium was measured by the luciferase assay. Results. In hypercalcemic rat, urinary ET-1 excretion was increased by twofold, and ET-1 mRNA expression was increased in the kidney cortex by threefold. In cortical collecting duct (CCD), both principal cells and intercalated cells synthesized ET-1. In cells that express CaR, ET-1 promoter was activated in a dose-dependent manner by extracellular calcium over the range of 0.5 to 3.0 mmol/L. Conclusions. First, activation of CaR increases ET-1 transcription in a dose-dependent manner. Second, hypercalcemia increases ET-1 production in the kidney cortex. These data suggest the possibility that CaR might play an important role in hypercalcemia-induced increase in ET-1 production.

Original languageEnglish (US)
Pages (from-to)845-852
Number of pages8
JournalKidney International
Volume63
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

Endothelin-1
Kidney
Calcium-Sensing Receptors
Hypercalcemia
Kidney Cortex
Luciferases
Dihydrotachysterol
Calcium
Natriuretic Agents
Polyuria
Messenger RNA
Natriuresis
COS Cells
Diuresis
Nephrons
Diuretics
Immunohistochemistry

Keywords

  • Calcium-sensing receptor
  • Endothelin
  • Hypercalcemia
  • Polyuria

ASJC Scopus subject areas

  • Nephrology

Cite this

Shiraishi, N., Kitamura, K., Kohda, Y., Narikiyo, T., Adachi, M., Miyoshi, T., ... Tomita, K. (2003). Increased endothelin-1 expression in the kidney in hypercalcemic rats. Kidney International, 63(3), 845-852. https://doi.org/10.1046/j.1523-1755.2003.00801.x

Increased endothelin-1 expression in the kidney in hypercalcemic rats. / Shiraishi, Naoki; Kitamura, Kenichiro; Kohda, Yukimasa; Narikiyo, Takefumi; Adachi, Masataka; Miyoshi, Taku; Iwashita, Kozo; Nonoguchi, Hiroshi; Miller, R. Tyler; Tomita, Kimio.

In: Kidney International, Vol. 63, No. 3, 01.03.2003, p. 845-852.

Research output: Contribution to journalArticle

Shiraishi, N, Kitamura, K, Kohda, Y, Narikiyo, T, Adachi, M, Miyoshi, T, Iwashita, K, Nonoguchi, H, Miller, RT & Tomita, K 2003, 'Increased endothelin-1 expression in the kidney in hypercalcemic rats', Kidney International, vol. 63, no. 3, pp. 845-852. https://doi.org/10.1046/j.1523-1755.2003.00801.x
Shiraishi N, Kitamura K, Kohda Y, Narikiyo T, Adachi M, Miyoshi T et al. Increased endothelin-1 expression in the kidney in hypercalcemic rats. Kidney International. 2003 Mar 1;63(3):845-852. https://doi.org/10.1046/j.1523-1755.2003.00801.x
Shiraishi, Naoki ; Kitamura, Kenichiro ; Kohda, Yukimasa ; Narikiyo, Takefumi ; Adachi, Masataka ; Miyoshi, Taku ; Iwashita, Kozo ; Nonoguchi, Hiroshi ; Miller, R. Tyler ; Tomita, Kimio. / Increased endothelin-1 expression in the kidney in hypercalcemic rats. In: Kidney International. 2003 ; Vol. 63, No. 3. pp. 845-852.
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abstract = "Background. Although hypercalcemia causes diuresis and natriuresis, the molecular mechanisms of these effects are not well established. Recently, the important role of the calcium-sensing receptor (CaR) in hypercalcemia-induced polyuria was reported. Endothelin-1 (ET-1) that is locally produced in the nephron has been suggested to have the natriuretic and/or diuretic effects in the kidney. Therefore, we hypothesized that ET-1 expression could be increased through the activation of CaR in the kidney in hypercalcemia. Methods. Rats were made hypercalcemic by dihydrotachysterol (DHT) treatment. The urinary concentration of ET-1 and the mRNA expression of ET-1 in the kidney were determined. Immunohistochemistry was performed to determine types of the cells that produce ET-1. CaR and ET-1 promoter luciferase constructs were co-expressed in COS-7 cells and the ET-1 promoter activity following the addition of extracellular calcium was measured by the luciferase assay. Results. In hypercalcemic rat, urinary ET-1 excretion was increased by twofold, and ET-1 mRNA expression was increased in the kidney cortex by threefold. In cortical collecting duct (CCD), both principal cells and intercalated cells synthesized ET-1. In cells that express CaR, ET-1 promoter was activated in a dose-dependent manner by extracellular calcium over the range of 0.5 to 3.0 mmol/L. Conclusions. First, activation of CaR increases ET-1 transcription in a dose-dependent manner. Second, hypercalcemia increases ET-1 production in the kidney cortex. These data suggest the possibility that CaR might play an important role in hypercalcemia-induced increase in ET-1 production.",
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AU - Shiraishi, Naoki

AU - Kitamura, Kenichiro

AU - Kohda, Yukimasa

AU - Narikiyo, Takefumi

AU - Adachi, Masataka

AU - Miyoshi, Taku

AU - Iwashita, Kozo

AU - Nonoguchi, Hiroshi

AU - Miller, R. Tyler

AU - Tomita, Kimio

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N2 - Background. Although hypercalcemia causes diuresis and natriuresis, the molecular mechanisms of these effects are not well established. Recently, the important role of the calcium-sensing receptor (CaR) in hypercalcemia-induced polyuria was reported. Endothelin-1 (ET-1) that is locally produced in the nephron has been suggested to have the natriuretic and/or diuretic effects in the kidney. Therefore, we hypothesized that ET-1 expression could be increased through the activation of CaR in the kidney in hypercalcemia. Methods. Rats were made hypercalcemic by dihydrotachysterol (DHT) treatment. The urinary concentration of ET-1 and the mRNA expression of ET-1 in the kidney were determined. Immunohistochemistry was performed to determine types of the cells that produce ET-1. CaR and ET-1 promoter luciferase constructs were co-expressed in COS-7 cells and the ET-1 promoter activity following the addition of extracellular calcium was measured by the luciferase assay. Results. In hypercalcemic rat, urinary ET-1 excretion was increased by twofold, and ET-1 mRNA expression was increased in the kidney cortex by threefold. In cortical collecting duct (CCD), both principal cells and intercalated cells synthesized ET-1. In cells that express CaR, ET-1 promoter was activated in a dose-dependent manner by extracellular calcium over the range of 0.5 to 3.0 mmol/L. Conclusions. First, activation of CaR increases ET-1 transcription in a dose-dependent manner. Second, hypercalcemia increases ET-1 production in the kidney cortex. These data suggest the possibility that CaR might play an important role in hypercalcemia-induced increase in ET-1 production.

AB - Background. Although hypercalcemia causes diuresis and natriuresis, the molecular mechanisms of these effects are not well established. Recently, the important role of the calcium-sensing receptor (CaR) in hypercalcemia-induced polyuria was reported. Endothelin-1 (ET-1) that is locally produced in the nephron has been suggested to have the natriuretic and/or diuretic effects in the kidney. Therefore, we hypothesized that ET-1 expression could be increased through the activation of CaR in the kidney in hypercalcemia. Methods. Rats were made hypercalcemic by dihydrotachysterol (DHT) treatment. The urinary concentration of ET-1 and the mRNA expression of ET-1 in the kidney were determined. Immunohistochemistry was performed to determine types of the cells that produce ET-1. CaR and ET-1 promoter luciferase constructs were co-expressed in COS-7 cells and the ET-1 promoter activity following the addition of extracellular calcium was measured by the luciferase assay. Results. In hypercalcemic rat, urinary ET-1 excretion was increased by twofold, and ET-1 mRNA expression was increased in the kidney cortex by threefold. In cortical collecting duct (CCD), both principal cells and intercalated cells synthesized ET-1. In cells that express CaR, ET-1 promoter was activated in a dose-dependent manner by extracellular calcium over the range of 0.5 to 3.0 mmol/L. Conclusions. First, activation of CaR increases ET-1 transcription in a dose-dependent manner. Second, hypercalcemia increases ET-1 production in the kidney cortex. These data suggest the possibility that CaR might play an important role in hypercalcemia-induced increase in ET-1 production.

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KW - Polyuria

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