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Regulation of acid secretion in cortical collecting duct : An Effect Mediated by Hensin.

Research Project

Project/Area Number 14571032
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionJichi Medical School

Principal Investigator

TSURUOKA Shuichi  Jichi Medical School, Medicine, Assistant Professor, 医学部, 講師 (50285798)

Co-Investigator(Kenkyū-buntansha) FUJIMURA Akio  Jichi Medical School, Medicine, Professor, 医学部, 教授 (90156901)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordscollecting duct / Hensin / metabolic acidosis / anion exchanger / cyclosporine A / Drug adverse reactions / 重炭酸
Research Abstract

Metabolic acidosis causes a reversal of polarity of HCO(3)(-) flux in the cortical collecting duct(CCD). In CCDs incubated in vitro in acid media, beta-intercalated (HCO(3)(-)-secreting) cells are remodeled to functionally resemble alpha-intercalated (H(+)-secreting) cells. A similar remodeling of beta-intercalated cells, in which the polarity of H(+) pumps and Cl(-)/HCO(3)(-) exchangers is reversed, occurs in cell culture and requires the deposition of polymerized hensin in the ECM. CCDs maintained 3 h at low pH ex vivo display a reversal of HCO(3)(-) flux that is quantitatively similar to an effect previously observed in acid-treated rabbits in vivo. We followed intracellular pH in the same beta-intercalated cells before and after acid incubation and found that apical Cl/HCO(3) exchange was abolished following acid incubation. Some cells also developed basolateral Cl(-)/HCO(3)(-) exchange, indicating a reversal of intercalated cell polarity. This adaptation required intact microtubules and microfilaments, as well as new protein synthesis, and was associated with decreased size of the apical surface of beta-intercalated cells. Addition of anti-hensin antibodies prevented the acid-induced changes in apical and basolateral Cl(-)/HCO(3)(-) exchange observed in the same cells and the corresponding suppression of HCO(3)(-) secretion. Acid loading also promoted hensin deposition in the ECM underneath adapting beta-intercalated cells. Hence, the adaptive conversion of beta-intercalated cells to alpha-intercalated cells during acid incubation depends upon ECM-associated hensin.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (23 results)

All 2005 2004 2003 2002 Other

All Journal Article (18 results) Publications (5 results)

  • [Journal Article] Cyclosporin produces distal Renal Tubular Acidosis by blocking peptidyl cis-trans prolyl isomerase activity of cyclophilin.2005

    • Author(s)
      Watanabe S, Tsuruoka S, et al.
    • Journal Title

      Am J Physiol Renal Physiol 288

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Treatment of digoxin intoxication model by hybrid kidney with hollowfiber module for clinical hemodialysis.2004

    • Author(s)
      Tsuruoka S, et al.
    • Journal Title

      Nephrol Dial Transplant 19

      Pages: 1339-1340

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chronopharmacology of oxacalcitriol in 5/6 nephrectomized rats2004

    • Author(s)
      Tsuruoka S, et al.
    • Journal Title

      Life Sci 75

      Pages: 809-822

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Treatment of digoxin intoxication model by hybrid kidney with hollowfiber module for clinical hemodialysis.2004

    • Author(s)
      Tsuruoka S, Nishiki K, Wakaumi M, Wang N, Yamamoto H, Ando H, Imai M, Fujimura A.
    • Journal Title

      Nephrol Dial Transplant 19(5)

      Pages: 1339-1340

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chronopharmacology of oxacalcitriol in 5/6 nephrectomized rats.2004

    • Author(s)
      Tsuruoka S, Nishiki K, Wakaumi M, Yamamoto H, Ando H, Wang N, Fujimura A.
    • Journal Title

      Life Sci. 75

      Pages: 809-822

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Treatment of digoxin intoxication model by hybrid-kidney with hollowfibre module for clinical haemodialysis.2004

    • Author(s)
      Tsuruoka S, et al.
    • Journal Title

      Nephrol Dial Transplant 19

      Pages: 1339-40

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Subclinical alteration of taste sensitivity induced by cande sartan in healthy subjects.2004

    • Author(s)
      Tsuruoka S, et al.
    • Journal Title

      Br J Clin Pharmacol 57

      Pages: 807-812

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chronopharmacology of oxacalcitriol in 5/6 nephrectomizedrats2004

    • Author(s)
      Tsuruoka S, et al.
    • Journal Title

      Life Sci 75

      Pages: 809-822

    • Related Report
      2004 Annual Research Report
  • [Journal Article] β2-microglobulin adsorption column reduces digoxin trough level during hemodialysis : 3 case reports.2004

    • Author(s)
      Tsuruoka S, et al.
    • Journal Title

      Ther.Drug Monit 26

      Pages: 450-452

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adsorption of oxacalcitriol by polysulfone hemodialyzer in patients with secondary hyperparathyroidism.2004

    • Author(s)
      Tsuruoka S, et al.
    • Journal Title

      Br J Clin Pharmacol 58

      Pages: 488-95

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibition of Rho-kinase reduces Na-H exchanger activity and natriuresis in rat.2003

    • Author(s)
      Nishiki, K., Tsuruoka, S et al.
    • Journal Title

      J Pharmacol Exp Ther 304

      Pages: 723-728

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nitric oxide production modulates cyclosporine A-induced distal renal tubular acidosis in the rat.2003

    • Author(s)
      Tsuruoka, S., Schwartz GJ, et al.
    • Journal Title

      J Pharmacol Exp Ther 305

      Pages: 840-845

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of Rho-kinase reduces Na-H exchanger activity and natriuresis in rat.2003

    • Author(s)
      Nishiki, K., Tsuruoka, S., Kawaguchi, A., Sugimoto, K., Imai, M., Fujimura A.
    • Journal Title

      J Pharmacol Exp Ther. 304

      Pages: 723-728

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nitric oxide production modulates cyclosporine A-induced distal renal tubular acidosis in the rat.2003

    • Author(s)
      Tsuruoka, S., Schwartz GJ, Wakaumi, M., Nishiki, K., Yamamoto H, Purkerson JM, Fujimura, A.
    • Journal Title

      J Pharmacol Exp Ther. 305

      Pages: 840-845

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Acid Incubation Reverses the Polarity of Intercalated Cell Transporters : An Effect Mediated by Hensin.2002

    • Author(s)
      Schwartz GJ, Tsuruoka S, Vijayakumar S et al.
    • Journal Title

      J.Clin.Invest. 109・1

      Pages: 89-99

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Apical H/base transporters mediating bicarbonate absorption and pHi regulation in outer medullary collecting duct.2002

    • Author(s)
      Yip, KP., Tsuruoka, S., Schwartz, GJ., Kurtz, I
    • Journal Title

      Am.J.Physiol.Renal Physiol. 283

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Al-Awqati' Q. Acid Incubation Reverses the Polarity of Intercalated Cell Transporters : An Effect Mediated by Hensin.2002

    • Author(s)
      Schwartz GJ, Tsuruoka S, Vijayakumar S, Petrovic S, Mian A
    • Journal Title

      J Clin.Invest. 109

      Pages: 89-99

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Apical H/base transporters mediating bicarbonate absorption and pHi regulation in outer medullary collecting duct..2002

    • Author(s)
      Yip, KP., Tsuruoka, S., Schwartz, GJ., Kurtz, I.
    • Journal Title

      Am J Physiol Renal Physiol. 283

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Nishiki, K., Tsuruoka, S et al.: "Inhibition of Rho-kinase reduces Na-H exchanger activity and natriuresis in rat."J Pharmacol Exp Ther. 304. 723-728 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuruoka, S., Schwartz GJ, et al.: "Nitric oxide production modulates cyclosporine A-induced distal renal tubular acidosis in the rat."J Pharmacol Exp Ther. 305. 840-845 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsumoto N, Tsuruoka S, et al.: "Expression of an artificial Cl channel in micro-perfused renal proximal tubules."J.Membr.Biol. 193. 195-200 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Schwartz GJ, Tsuruoka S, Vijayakumar S, et al.: "Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin"J.Clin.Invest.. 109・1. 89-99 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yip, KP., Tsuruoka, S., Schwartz, GJ., Kurtz I: "Apical H/base transporters mediating bicarbonate absorption and pHi regulation in the outer medullary collecting duct"Am.J.Physiol.Renal Physiol.. 283. F1098-F1104 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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