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pH-sensitive expression of calcium-sensing receptor (CaSR) in type-B intercalated cells of the cortical collecting ducts (CCD) in mouse kidney

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Abstract

Background

The localization and role of the calcium-sensing receptor (CaSR) along the nephron including the collecting ducts is still open to debate.

Methods

Using the quantitative, highly sensitive in situ hybridization technique and a double-staining immunohistochemistry technique, we investigated the axial distribution and expression of CaSR along the nephron in mice (C57B/6J) treated for 6 days with acid or alkali diets.

Results

Under control condition, CaSR was specifically localized in the cortical and medullary thick ascending limb of Henle’s loop (CTAL and MTAL), macula densa (MD), distal convoluted tubule (DCT), and CCD (TALs, MD > DCT, CCD). Along the CCD, CaSR was co-localized with an anion exchanger type 4 (AE4), a marker of the basolateral membrane of type-B intercalated cell (IC-B) in mice. On the contrary, CaSR was not detected either in principal cells (PC) or in type-A intercalated cell (IC-A). CaSR expression levels in IC-B significantly (P < 0.005) decreased when mice were fed NH4Cl (acid) diets and increased when animals were given NaHCO3 (alkali) diets. As expected, cell heights of IC-A and IC-B significantly (P < 0.005) increased in the above experimental conditions. Surprisingly, single infusion (ip) of neomycin, an agonist of CaSR, significantly (P < 0.005) increased urinary Ca excretion without further increasing the hourly urine volume and significantly (P < 0.05) decreased urine pH.

Conclusion

CaSR, cloned from rat kidney, was localized in the basolateral membrane of IC-B and was more expressed during alkali-loading. Its alkali-sensitive expression may promote urinary alkali secretion for body acid–base balance.

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Acknowledgments

This study was supported by grants from the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Y.Y. (No. 24790222) and to K.K. (No. 23591224, 26461259). Special thanks are given to Y.Nakabayashi (Kitasato Univ Sch of Med) for her technical assistance. Parts of this study were presented at the meetings of American Society of Nephrology (Philadelphia, 2011) and International Union of Physiological Sciences (Birmingham (UK), 2013).

Conflict of interest

The authors have declared that no conflict of interest exists.

Author information

Authors and Affiliations

  1. Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan

    Yukiko Yasuoka & Katsumasa Kawahara

  2. Department of Cellular and Molecular Physiology, Kitasato University Graduate School of Medical Sciences, Sagamihara, 252-0374, Japan

    Yukiko Yasuoka & Katsumasa Kawahara

  3. Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara, 252-0374, Japan

    Yuichi Sato

  4. ALESS Program, Komaba Organizational for Educational Excellence, College of Art and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan

    Jillian M. Healy

  5. Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto, 364-8501, Japan

    Hiroshi Nonoguchi

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  1. Yukiko Yasuoka
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Correspondence to Katsumasa Kawahara.

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Yasuoka, Y., Sato, Y., Healy, J.M. et al. pH-sensitive expression of calcium-sensing receptor (CaSR) in type-B intercalated cells of the cortical collecting ducts (CCD) in mouse kidney. Clin Exp Nephrol 19, 771–782 (2015). https://doi.org/10.1007/s10157-014-1063-1

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  • DOI: https://doi.org/10.1007/s10157-014-1063-1

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