2004 Fiscal Year Final Research Report Summary
Regulation of acid secretion in cortical collecting duct : An Effect Mediated by Hensin.
| Project/Area Number |
14571032
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Jichi Medical School |
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Principal Investigator |
TSURUOKA Shuichi Jichi Medical School, Medicine, Assistant Professor, 医学部, 講師 (50285798)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMURA Akio Jichi Medical School, Medicine, Professor, 医学部, 教授 (90156901)
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| Project Period (FY) |
2002 – 2004
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| Keywords | collecting duct / Hensin / metabolic acidosis / anion exchanger / cyclosporine A / Drug adverse reactions |
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| 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.
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[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.
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Journal Title
J Pharmacol Exp Ther. 304
Pages: 723-728
Description
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[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.
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Journal Title
J Pharmacol Exp Ther. 305
Pages: 840-845
Description
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