title: pH-sensitive expression of calcium-sensing receptor (CaSR) in type-B intercalated cells of the cortical collecting ducts (CCD) in mouse kidney.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan.|Department of Cellular and Molecular Physiology, Kitasato University Graduate School of Medical Sciences, Sagamihara, 252-0374, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yasuoka
authors.affiliation: Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara, 252-0374, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: 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.
authors.forename: Jillian M
authors.initials: JM
authors.lastname: Healy
authors.affiliation: Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto, 364-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonoguchi
authors.affiliation: Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan. kawahara@kitasato-u.ac.jp.|Department of Cellular and Molecular Physiology, Kitasato University Graduate School of Medical Sciences, Sagamihara, 252-0374, Japan. kawahara@kitasato-u.ac.jp.
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kawahara
mesh_terms: D000818:Animals; D002118:Calcium / Q000652:urine; D048429:Cell Size; D004232:Diuretics / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D017403:In Situ Hybridization; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009399:Nephrons / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C577923:CASR protein, mouse; D004232:Diuretics; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled; D002118:Calcium
keywords: Acid/base diet; Calcium-sensing receptor; Kidney collecting duct intercalated cell; Neomycin; Urinary calcium concentration