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Regulated expression and functional modulation of norepinephrine transporter by isoform interaction

Research Project

Project/Area Number 13680844
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOKAYAMA UNIVERSITY (2002)
Hiroshima University (2001)

Principal Investigator

KITAYAMA Shigeo  Okayama University, Graduate School of Medicine and Dentistry, professor, 大学院・医歯学総合研究科, 教授 (80177873)

Co-Investigator(Kenkyū-buntansha) MORITA Katsuya  Hiroshima University, Graduate School of Biomedical Sciences, associate professor, 大学院・医歯薬学総合研究科, 助教授 (10116684)
DOHI Toshihiro  Hiroshima University, Graduate School of Biomedical Sciences, professor, 大学院・医歯薬学総合研究科, 教授 (00034182)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsnorepinephrine / transporter / neurotransmitter / alternative splicing / antidipressant
Research Abstract

To explore the possible interaction between isoforms of norepinephrine transporter (NET) produced by alternative splicing for their functional expression, we first identified a series of NET splice variants from human and cow. By comparing 3'-flanking region of both NET gene encoding COOH terminal region, it was demonstrated that organization of human and bovine NET gene displays similar structure, which consists of cassettes C0, C1, C2 and C3 from exon 13〜16. Alternative splicing occurs at this region by selection of exon 15 or 16 and inclusion/exclusion of exon 14, resulting in types 1a (C0-C1-C2), 1b (C0-C2), 2a (C0-C1-C3), 2b (C0-C3). Human NET reveals 1a and 2a, but not 1b or 2b, whereas bovine NET shows all isoforms. In human NET, one additional isoform, designated type 2c, exists, which results from alternative cassette C3' encoded by exon 16 at 12nt upstream resulting in another COOH terminal composed of 3 amino acids. Both type 1a and 2a revealed functional expression, while type 1b, 2b and 2c lacked transport activity when expressed transiently in COS-7 cells. Taken together with our previous findings of rat NET isoforms produced by alternative splicing, it is concluded that these isoforms reveal different functional properties and regulated expression, and that interaction between isofoms produces regulation of their functional expression probably at various steps including membrane trafficking, oligomerization and functional coupling.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Shigeo kitayama et al.: "Identification and functional characterization of the novel isoforms of bovine norepinephrine transporter produced by alternative splicing"Brain Res.. 934. 152-156 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshihiro Dohi et al.: "Inhibition of monoamine neurotransmitter transporter and central nervous system stimulation induced by synthetic local anesthetics and cocaine : a"Current Medicinal Chemistry-Central Nervous System Agents : Mini-Review. 2. 295-315 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigeo Kitayama et al.: "Functional characterization of the splicing variants of human norepinephrine transporter"Neurosci.Lett.. 312. 108-112 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mitsutaka Sugimura et al.: "Effects of volatile and intravenous anesthetics on the uptake of GABA glutamate and dopamine by their transporters heterologously expressed in COS cells and in rat brain synaptosomes"Toxicol.Lett.. 123. 69-76 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 北山滋雄, 土肥敏博(分担執筆): "「d.ノルエピネフリン」の項(pp440-447)。澤田康文編「薬物動態・作用と遺伝子多型」"医薬ジャーナル社. 457 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigeo Kitayama, Kei Kumagai, Katsuya Morita and Toshihiro Dohi: "Identification and functional characterization of the novel isoforms of bovine norepinephrine transporter produced by alternative splicing"Brain.Res.. 934. 152-156 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshihiro Dohi, Shigeo Kitayama, Katsuya Morita, Tomoyuki Sato, Shigeaki Arai, Kei Kumagai, Wataru Hashimoto and Kenji Kihira: "Inhibition of monoamine neurotransmitter transporter and central nervous system stimulation induced by synthetic local anesthetics and cocaine : a comparative review"Current Medicinal Chemistry-Central Nervous System Agents : Mini-Review. 2. 295-315 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigeo Kitayama, Katsuya Morita and Toshihiro Dohi: "Functional characterization of the splicing variants of human norepinephrine transporter"Neurosci.Lett.. 312. 108-112 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mitsutaka Sugimura, Shigeo Kitayama, Katsuya Morita, Masahiro Irifune, Tohru Takarada, Michio Kawahara and Toshihiro Dohi: "Effects of volatile and intravenous anesthetics on the uptake of GABA, glutamate and dopamine by their transporters heterologously expressed in COS cells and in rat brain synaptosomes"Toxicol.Lett.. 123(1). 69-76 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigeo kitayama et al.: "Identification and functional characterization of the novel isoforms of bovine norepinephrine transporter produced by alternative splicing"Brain Res.. 934. 152-156 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Kitayama et al.: "Functional characterization of the splicing variants of human norepinephrine transporter"Neurosci. Lett.. 312. 108-112 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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