• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Regulation of tetrahydrobiopterin and monoamine transport by cyclic GMP

Research Project

Project/Area Number 14571774
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionMeikai University

Principal Investigator

NAKANISHI Nobuo  Meikai University, School of Dentistry, Biochemistry, Lecturer, 歯学部, 講師 (20118574)

Co-Investigator(Kenkyū-buntansha) KURIHARA Kinji  Meikai University, School of Dentistry, Physiology, Assistant, 歯学部, 助手 (10170086)
HASEGAWA Hiroyuki  Teikyo University, Science and Technology, Bioscience, Professor, 理工学部, 教授 (10092983)
OGURO Kazuya  Teikyo University, Science and Technology, Bioscience, Assistant, 理工学部, 助手 (00233081)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordscyclic GMP / cyclic AMP / vesicular monoamine transporter / tetrahydrobiopterin / nitric oxide synthase / dopamine / serotonine / neurotransmitter
Research Abstract

We found that the vesicular monoamine transport activity of neuronal cell line, PC12, was stimulated by cyclic GMP (cGMP) while it was inhibited by cyclic AMP (cAMP). We also found that both cGMP and cAMP down-regulated the transport of tetrahydrobiopterin (BH4), a cofactor for nitric oxide synthase and for aromatic amino acid hydroxylases, through plasma membranes of various cells. In this works, we examined the mechanisms of BH4 transport and the effects of cGMP on the BH4 transport and on the vesicular monoamine transport.
1.BH4 transport : Outward flow of endogenous BH4 to extracellular fluid and inward flow of exogenous BH4 into the cells were mediated by different transport systems. Three pathways were found to be present for BH4 outward flow : 1)a pathway by transporter belonged to ion gradient-dependent toxin-extruding antiporter (TEXAN) family. This type of BH4 transporter was down-regulated by cGMP. 2)a pathway which was sensitive to osmotic pressure and involved a membrane protein belonged to aquaporin family for BH4 transport. This pathway was therefore regulated by Na+-K+-ATPase and ion transporters for K+ and Cl- ions. 3)a pathway mediated by a member of ABC transporter family such as multi-drug resistant protein (MDR).
On the other hand, BH4 transporter which is responsible for exogenous BH4 uptake into cytoplasm was specifically present in intestinal epithelial cells and in kidney. This type of BH4 transport activity was also detected in erythrocytes.
2.Vesicular monoamine transport : Vesicular monoamine transport was up-regulated by cGMP in a dose-dependent manner. Phosphorylation of the vesicular monoamine transporter (VMAT) molecules by cGMP was not detected. cGMP seemed to affect the targeting of VMAT molecules to the vesicular membranes. Studies is in progress to search proteins which might be involved in the VMAT targeting to the secretory vesicle membranes as a mediater of cGMP effect.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (45 results)

All 2005 2003 2002 Other

All Journal Article (32 results) Book (4 results) Publications (9 results)

  • [Journal Article] Increase in tetrahydrobiopterin release from PC12 cells under hypotonic culture conditions is inhibited by HgCl_<2->2005

    • Author(s)
      Nakanishi, N.
    • Journal Title

      Pteridines 16

      Pages: 1-5

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Supplementation with tetrahydrobiopterin prevents the cardiovascular effects of angiotensin II-induced oxidative and nitrosative stress.2005

    • Author(s)
      Kase, H.
    • Journal Title

      J. Hypertension 23

      Pages: 1375-1382

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Delivery of tetrahydrobiopterin (BH_4) to cells of target organs : Role of salvage pathway and uptake of its precursor in effective elevation of tissue BH_<4-> [Review]2005

    • Author(s)
      Hasegawa, H.
    • Journal Title

      Mol. Genet. Metab. 86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cellular accumulation of tetrahydrobiopterin following its administration is mediated by two different processes; direct uptake and indirect uptake mediated by a methotrexate-sensitive process.2005

    • Author(s)
      Sawabe, K.
    • Journal Title

      Mol. Genet. Metab. 86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increase in tetrahydrobiopterin release from PC12 cells under hypotonic culture conditions is inhibited by HgCl_2.2005

    • Author(s)
      Nakanishi, N., Kurihara, K., Tomomura, A., Tonosaki, K., Hattori, Y., Oguro, K., Hasegawa, H
    • Journal Title

      Pteridines 16

      Pages: 1-5

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Supplementation with tetrahydrobiopterin prevents the cardiovascular effects of angiotensin II-induced oxidative and nitrosative stress.2005

    • Author(s)
      Kase, H., Hashikabe, Y., Kohsuke Uchida, K., Nakanishi, N., Hattori, Y.
    • Journal Title

      J.Hypertension 23

      Pages: 1375-1382

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Delivery of tetrahydrobiopterin (BH_4) to cells of target organs : Role of salvage pathway and uptake of its precursor in effective elevation of tissue BH_4.2005

    • Author(s)
      Hasegawa, H., Sawaba, K., Nakanishi, N., Wakasugi, O.K.
    • Journal Title

      Mol.Genet.Metab.[Review] 86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cellular accumulation of tetrahydrobiopterin following its administration is mediated by two different processes ; direct uptake and indirect uptake mediated by a methotrexate-sensitive process.2005

    • Author(s)
      Sawabe, K., Suetake, Y., Nakanishi, N., Wakasugi, K.O., Hasegawa, H.
    • Journal Title

      Mol.Genet.Metab. 86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increase in tetrahydrobiopterin release from PC12 cells under hypotonic culture conditions is inhibited by HgCl_22005

    • Author(s)
      Nakanishi, N.
    • Journal Title

      Pteridines 16・1

      Pages: 1-5

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Supplementation with tetrahydrobiopterin prevents the cardiovascular effects of angiotensin II-induced oxidative nitrosative stress2005

    • Author(s)
      Kase, H.
    • Journal Title

      Journal of Hypertension 23・7

      Pages: 1375-1382

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Delivery of exogenous tetrahydrobiopterin(BH_4)to cells of target organs : Role of salvage pathway and uptake of its precursor in effective elevation of tissue BH_42005

    • Author(s)
      Hasegawa, H.
    • Journal Title

      Molecular Genetics and Metabolism 86

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cellular accumulation of tetrahydrobiopterin following its administration is mediated by two different processes ; direct uptake and indirect uptake mediated by a methotrexate-sensitive process2005

    • Author(s)
      Sawabe, K.
    • Journal Title

      Molecular Genetics and Metabolism 86

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increase in tetrahydrobiopterin release from PC12 cells under hypotonic culture conditions is inhibited by HgCl_22005

    • Author(s)
      Nakanishi, N.
    • Journal Title

      Pteridines 16(in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Na^+-K^+-2Cl^- 共輸送およびアミン輸送の調節 : cAMPの作用〔総説〕2003

    • Author(s)
      栗原琴二
    • Journal Title

      日本唾液腺学会誌 44

      Pages: 1-14

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Specific expression of an A-kinase anchoring protein subtype, AKAP-150, and specific regulatory mechanism for Na^+, K^+-ATPase via protein kinase A in the parotid gland among the three major salivary glands of the rat.2003

    • Author(s)
      Kurihara, K.
    • Journal Title

      Biochem Pharmacol. 66

      Pages: 239-250

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells.2003

    • Author(s)
      Hattori, Y.
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol. 23

      Pages: 176-182

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Exogenous biopterin requirment for iNOS function in vascular smooth muscle cells.2003

    • Author(s)
      Yoshida, M.
    • Journal Title

      J. Cardiovasc. Pharmacol. 42

      Pages: 197-203

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of Na+-K+-2Cl- cotransporter and of monoamine transporters : effects of cyclic AMP. [Review in Japanese]2003

    • Author(s)
      Kurihara, K., Nakanishi, N.
    • Journal Title

      Jpn.J.Salivary Glands 44

      Pages: 1-14

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Specific expression of an A-kinase anchoring protein subtype, AKAP-150, and specific regulatory mechanism for Na^+, K^+ -ATPase via protein kinase A in the parotid gland among the three major salivary glands of the rat.2003

    • Author(s)
      Kurihara, K., Nakanishi, N., Amano, O., Yamamoto, M., Iseki, S.
    • Journal Title

      Biochem Pharmacol. 66

      Pages: 239-250

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells.2003

    • Author(s)
      Hattori, Y., Nakanishi, N., Akimoto, K., Yoshida, M., Kasai, K.
    • Journal Title

      Arterioscler.Thromb.Vasc.Biol. 23

      Pages: 176-182

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Exogenous biopterin requirment for iNOS function in vascular smooth muscle cells.2003

    • Author(s)
      Yoshida, M., Nakanishi, N., Wang, X., Hattori, Y.
    • Journal Title

      Cardiovasc.Pharmacol. 42

      Pages: 197-203

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulatory effect of cyclic AMP on transport of biogenic amines and of inorganic ions.2003

    • Author(s)
      Kurihara, K., Hasegawa, H., Nakanishi, N.
    • Journal Title

      In : Recent Research Developments in Biochemistry, Research Signpost, Kerala, India.[Book] Vol.4

      Pages: 303-334

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of Na^+, K^+ -ATPase by cAMP-dependent protein kinase anchored on membrane via A-kinase anchoring protein subtype, AKAP-150, in rat parotid gland.2003

    • Author(s)
      Kurihara, K., Nakanishi, N.
    • Journal Title

      In : Annuals of the New York Academy of Science [Book] Vol.986

      Pages: 636-638

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increase in the biopterin pool after tetrahydrobiopterin administration is due to uptake of an oxidation product dihydrobiopterin and its conversion to the reduced state.2003

    • Author(s)
      Sawabe, K., Yamamoto, K., Matsuhashi, Y., Miura, H., Wakasugi, K.O., Nakanishi, N., Hasegawa, H.
    • Journal Title

      In : Pterines, Folates and Neurotransmitters in Molecular Medicine.(Blau, N. and Thony, B. eds.) (SPS Publications, Heilbronn, Germany) [Book]

      Pages: 41-47

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phosphorylation of the salivary Na^+-K^+-2Cl^- cotransporter.2002

    • Author(s)
      Kurihara K.
    • Journal Title

      Am. J. Physiol. Am. J. Physiol. (Cell Physiol.) 282

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors enhance cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells.2002

    • Author(s)
      Hattori, Y.
    • Journal Title

      Pteridines 13

      Pages: 26-31

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Statin enhances cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells.2002

    • Author(s)
      Hattori, Y.
    • Journal Title

      Cardiovasc. Res. 54

      Pages: 659-658

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Proteasome driven turnover of tryptophan hydroxylase is triggered by phosphorylation in RBL2H3 cells, a serotonin producing mast cell line.2002

    • Author(s)
      Iida, Y.
    • Journal Title

      Eur. J. Biochem. 269

      Pages: 4780-4788

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phosphorylation of the salivary Na^+-K^+-2Cl^- cotransporter.2002

    • Author(s)
      Kurihara K., Nakanishi N., Moore-Hoon M.L., Turner R.J.
    • Journal Title

      Am.J.Physiol.(Cell Physiol.) 282

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors enhance cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells2002

    • Author(s)
      Hattori, Y., Nakanishi, N., Suzuki, M., Yoshida, M., Kasai, K.
    • Journal Title

      Pteridines 13

      Pages: 26-31

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Statin enhances cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells.2002

    • Author(s)
      Hattori, Y., Nakanishi, N., Kasai, K.
    • Journal Title

      Cardiovasc.Res. 54

      Pages: 649-658

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Proteasome driven turnover of tryptophan hydroxylase is triggered by phosphorylation in RBL2H3 cells, a serotonin producing mast cell line.2002

    • Author(s)
      Iida, Y., Sawaba, K., Oguro, K., Nakanishi, N., Hasegawa, H.
    • Journal Title

      Eur.J.Biochem. 269 (19)

      Pages: 4780-4788

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Regulatory effect of cyclic AMP on transport of biogenic amines and of inorganic ions. In : Recent Research Developments in Biochemistry, Vol.4 (Kerala, India)2003

    • Author(s)
      Kurihara, K.
    • Total Pages
      32
    • Publisher
      Research Signpost.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Regulation of Na^+, K^+-ATPase by cAMP-dependent protein kinase anchored on membrane via A-kinase anchoring protein subtype, AKAP-150, in rat parotid gland. Ann. N.Y. Acad. Sci. Vol. 9862003

    • Author(s)
      Kurihara, K.
    • Total Pages
      3
    • Publisher
      The New York Academy of Sciences.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Increase in the biopterin pool after tetrahydrobiopterin administration is due to uptake of an oxidation product dihydrobiopterin and its conversion to the reduced state. In : Pterines, Folates and Neurotransmitters in Molecular Medicine (Heilbronn, Germany)2003

    • Author(s)
      Sawabe, K.
    • Total Pages
      7
    • Publisher
      SPS Publications
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Pterines, Folates and Neurotransmitters in Molecular Mediine. (Blau, N. and Tho"ny, B. eds.)2003

    • Author(s)
      Sawabe, K.
    • Publisher
      SPS Publications, Heilbronn, Germany
    • Related Report
      2004 Annual Research Report
  • [Publications] Hattori, Y.: "HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells."Arteriosclerosis, Thrombosis, and Vascular Biology. 23. 176-182 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurihara, K.: "Specific expression of an A-kinase anchoring protein subtype, AKAP-150, and specific regulatory mechanism for Na+,K+-ATPase via protein kinase A in the parotid gland among the three major salivary glands of the rat."Biochemical Pharmacology. 66. 239-250 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshida, M.: "Exogenous biopterin requirment for iNOS function in vascular smooth muscle cells."Journal of Cardiovascular Pharmacology. 42. 197-203 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 栗原琴二: "Na^+-K^+-2Cl^-共輸送およびアミン輸送の調節:cAMPの作用[総説]"日本唾液腺学会誌. 44. 1-14 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurihara, K.: "Regulatory effect of cyclic AMP on transport of biogenic amines and of inorganic ions."Recent Research Developments in Biochemistry (Pandalai, S.G., ed) (Research Signpost, Kerala, India). Vol.4. 32 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurihara, K.: "Regulation of Na+,K+-ATPase by cAMP-dependent protein kinase anchored on membrane via A-kinase anchoring protein subtype, AKAP-150, in rat parotid gland."Na,K-ATPase and Related Cation Pumps. Annals of the New York Academy of Sciences (Jorgensen, P.L., Karlish, S.J.D. & Maunsbach, A.B., eds). Vol.986. 3 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hattori, Y.: "3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors enhance cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells"Pteridines. 13. 26-31 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hattori, Y.: "Statin enhances cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells"Cardiovascular Research. 54. 649-658 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] lida, Y.: "Proteasome driven turnover of tryptophan hydroxylase is triggered by phosphorylation in RBL2H3 cells, a serotonin producing mast cell line"European Journal of Biochemistry. 269. 4780-4788 (2002)

    • Related Report
      2002 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi