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1999 Fiscal Year Final Research Report Summary

Regulation and effects of intracellular Cl concentrations

Research Project

Project/Area Number 09470027
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKansai Medical University

Principal Investigator

INAGAKI Chiyoko  Kansai Medical University, Department of Pharmacolgy, Professor, 医学部, 教授 (60025640)

Co-Investigator(Kenkyū-buntansha) OTANI Hitomi  Kansai Medical University, Department of Pharmacolgy, Assistant Professor, 医学部, 講師 (40140272)
HARA Mitsuyoshi  Kansai Medical University, Department of Pharmacolgy, Assistant Professor, 医学部, 講師 (50192282)
OMORI Kyoko  Kansai Medical University, Department of Pharmacolgy, Associate Professor, 医学部, 助教授 (90152256)
KITAGAWA Kaori  Kansai Medical University, Department of Pharmacolgy, Research Associate, 医学部, 助手 (10165813)
HATTORI Naoki  Kansai Medical University, Department of Pharmacolgy, Assistant Professor, 医学部, 講師 (80288828)
Project Period (FY) 1997 – 1999
Keywordschloride ion / c-fos expression / brain / ammonia / anion exhanger / protein kinase C / hypoxia / chloride pump
Research Abstract

(1) Intraneuronal ClィイD1=ィエD1 concentrations ([ClィイD1=ィエD1]i) and immediately early gene (c-fos) expression
Intracerebroventricular administration of a ClィイD1-ィエD1 pump inhibitor, ethacrynic acid, caused convulsions in mice. Expression of c-fos was stimulated biphasically with the peaks at 60min and 10-14 days after the convulsion. Expression of nerve growth factor, damage of GABAergic neurons and development of seizure susceptibility were also observed. A transient increase in neuronal [ClィイD1-ィエD1]i thus appeared to cause biphasic increases in c-fos expression and related modulation of neuronal functions.
(2) Mechanisms of ammonia-induced increases in neuronal [ClィイD1=ィエD1]i
A neurotoxic factor in hepatic encephalopathy, ammonia (2 mM, 48 hr), increased [ClィイD1-ィエD1]i in cultured rat hippocampal neurons. The increase was found to be due to enhanced expression of anion exchanger (AE3) mediated by protein kinase C activation.
(3) ClィイD1=ィエD1 transport in hypoxia/reoxygenaion-induced changes in pHi and {CaィイD12+ィエD1]i in myocytes
Under hypoxia/reoxygenaion conditions, pHi decreased and [CaィイD12+ィエD1]i increased during hypoxia and reoxygenation, respectively. Inhibitors of anion exchanger (SITS and DIDS) and removal of medium ClィイD1-ィエD1 or HCOィイD23ィエD2 attenuated such changes in pHi and [CaィイD12+ィエD1]i. Inhibitors of protein kinase C slightly reduced the changes in pHi. Involvement of anion exchanger in hypoxia-induced pHi changes was first demonstrated with the resulting inhibitory effects on reoxygenation-induced increases in [CaィイD12+ィエD1]i.
(4) Subunits and cDNA cloning of neuronal ClィイD1=ィエD1 pump
A new ClィイD1-ィエD1 transporter, ClィイD1-ィエD1 pump, was isolated as 520 kDa protein complex from the rat brain. SDS-PAGE analyses yielded 4 subunits (51, 55, 60 and 62kDa), and 51kDa protein appeared to be a catalytic subunit. cDNA for 55 kDa protein was cloned from the rat brain cDNA library, and its primary structure was assumed to be a new peptide with 475 amino acids.

  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Irie, T. et al.: "Chloride concentration in cultured hippocompal・・"Brain Research. 806. 246-256 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hattori N. et al.: "Cl^--ATPase and Na^+, K^+-ATPase actiocties in・・"Neuroscience Research. 254. 141-144 (1998)

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      「研究成果報告書概要(和文)」より
  • [Publications] Zeng X. et al.: "Antiserum against Cl^- pump complex・・・"Neuroscience Research. 258. 85-88 (1998)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki E. et al.: "Single cell RT-PCR demonstrates expression of"Brain Research. 838. 166-170 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Suzukawa J. et al.: "Long-lasting c-fos and NGF mRNA expression・・"Brain Research. 834. 89-102 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Yagyu K. et al.: "Lithium decreases Cl^--ATPase activity・・"Brain Research. 821. 530-534 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 稲垣千代子: "脳機能の解明(分担)"九州大学出版会(赤池紀扶他編). 9 (1998)

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  • [Publications] 稲垣千代子他: "生体の科学(神経系に作用する薬物マニュアル)(分担)"金原一郎記念医療振興財団/医学書院. 3 (1998)

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  • [Publications] Tanabe, T., Otani, H., Mishima, K., Ogawa, R. and Inagaki, C.: "Phorbol-12-myristate-13-acetate (PMA)-induced oxyradical production in rheumatoid synovial cells."Jpn. J. Pharmacol.. 73. 347-351 (1997)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Hattori, N. and Inagaki, C.: "Anti-prolactin autoanntibodies cause asymptomatic hyperprolactinemia : Bioassay and clearance studies of PRI-IgG complex."J. Clin. Endocr. Metab.. 62. 3107-3110 (1997)

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  • [Publications] Minamino, M., Hara, M. Ohnishi, S. Irie, T., Yamashita, T., Minato, A. and Inagaki, C.: "Effects of protein kinase and phosphatase inhibitors on slow shortening of guine a pig cochlear outer hair cells."Brain Res.. 781. 275-283 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Irie, T., Hara, M., Yasukura, T., Minamino, M., Omori, K., Matsuda, H., Inoue, K. and Inagaki, C.: "Chloride concentration in cultured hippocampal neurons increases during long-term exposure to ammonia through expression of anion exchanger."Brain Res.. 806. 246-256 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hattori, N., Kitagawa, K., Higashida, T., Yagyu, K., Shimohama, S., Takaya, T., Perry, G., Smith, M. A. and Inagaki, C.: "ClィイD1-ィエD1-ATPase and NaィイD1+ィエD1, KィイD1+ィエD1-ATPase activities in Alzheimer's disease brains."Neurosci. Lett.. 254. 141-144 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Hattori, N. and Inagaki, C.: "Immunological aspects of human growth hormone and prolactin."Domestic Animal Endocrynology. 15. 371-375 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Zeng, X.-T., Higashida, T., Hara, M., Hattori, N., Kitagawa, K., Omori, K. and Inagaki, C.: "Antiserum against ClィイD1-ィエD1 pump complex recognized 51 kDa protein, a posible catalytic unit in the rat brain."Neurosci. Lett.. 258. 85-88 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujiseki, Y., Omori, K., Omori, K., Mikami, Y., Suzukawa, J., Okugawa, G., Uyama, M. and Inagaki, C.: "Natriuretic peptide receptors, NPR-A and NPR-B, on cultured rabbit retinalpigment epithelial cells."Jpn. J. Pharmacol.. 79. 359-368 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kawasaki, E., Hattori, N., Miyamoto, E., Yamashita, T. and Inagaki, C.: "Single-cell RT-PCR demonstrates expression of voltage-dependent chloride channels (ClC-1, ClC-2 and ClC-3) in outer hair cells of rat cochlea."Brain Res.. 838. 166-170 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzukawa, J., Omori, K., Okugawa, G., Fujiseki, Y., Heizmann, C. W. and Inagaki, C.: "Long-lasting c-fons and NGF mRNA expressions and loss of perikaryal parvalbumin immunore activity in the development of epileptogenesis after ethacrynic acid-induced seizure."Brain Res.. 834. 89-102 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Okugawa, G., Omori, K., Suzukawa, J., Fujiseki, Y., Kinoshita, T. and Inagaki, C.: "Long-term treatment with antidepressants increases glucocorticoid receptor binding and gene expression in cultured rat hippocampal neurons."J. Neuroendocrinol.. 11. 887-895 (1999)

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  • [Publications] Hattori, N., Kaori Kitagawa and Chiyoko Inagaki: "Human lymphocytes express hGH-N gene transcripts of 22kDa, 20kDa and minor forms of GH, but not hGH-V gene."Eur. J. Endocrinol.. 141. 413-418 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Yagyu, K., Kitagawa, K., Irie, T., Hattori, N., Omori, K., Inagaki, C.: "Lithium decreases ClィイD1-ィエD1-ATPase activity and increases intracellular ClィイD1-ィエD1 concentration in cultured rat hippocampal neurons."Brain Res.. 821. 530-534 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Omori, K. Inagaki, C., Sasa, M.: "Molecular mechanisms underlying epileptic seizure"Folia pharmacologica japonica. 114. 161-168 (1999)

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  • [Publications] Mishima, K., Otani, H., Tanabe, T., Kawasaki, H., Saito, N., Ogawa, R. and Inagai, C.: "Molecular mechanisms for α2-adrenoceptor-mediated regulation of synoviocyte populations."Arthritis Rheum. (revision submitted).

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Published: 2001-10-23  

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