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Molecular recognition of vasoactive peptides : basis for Physiological action

Research Project

Project/Area Number 05044192
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionNagoya University

Principal Investigator

NARUSE Satoru  Nagoya University School of Medicine, Lecturer, 医学部, 講師 (50180550)

Co-Investigator(Kenkyū-buntansha) HERBST F.  Biotek Institut, Head, 所長
FORSSMANN W.g.  Niedersachsisches Institut fur Peptid-Forschung, Professor, 所長教授
WARY Victor  Gesellschaft fur Biotechnologische Forschung, Head, 室長
NOKIHARA Kiyoshi  Shimazu Corp.Biotechnology Instr.Dept., Head, バイオ機器部, 研究開発専門部長 (60137073)
OZAKI Tsuyoshi  National Institute for physiological Sciences, Associate Professor, 生理学研究所, 助教授 (20045694)
FURUYA Sonoko  National Institute for physiological Sciences, Instructor, 生理学研究所, 助手 (20096952)
FORSSMANN W.  ニーダーザクセン州立ペプチド研究所, 所長 教授
VICTOR Wray  国立バイオテクノロジー研究所, 主任 研究員
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsPACAP / PRP / endothelin / secretin / receptor / NMR spectroscopy / radioimmunoassay / 受容体 / セクレチン / NMRスペクトル / 構造活性相関
Research Abstract

The structure of pituitary adenylate activating polypeptide (PACAP) and (PACAP) related peptide (PRP) were investigated by CD and NMR spectroscopy, distance geometry, molecular dynamics and energy minimization calculations. PACAP38 and 27 had an initial disordered N-terminal structure, followed by a helical structures. PRP had a helical structure from 3-20th. Based on these results, several PACAP related peptides were synthesized by a solid phase peptide synthesizer. PACAP was a potent vosodilator. Vascular effects of PACAP was independent of the endothelium and was not blocked by NO synthase inhibitors.
PACAP37,36,35,34, and 33 had similar peak vascular effects to PACAP38 but the duration of action was dependent on the length of the peptide. PACAP had an opposite effect to VIP on the guinea pig gallbladder. The C-terminus of PACAP and VIP,where two peptides show the largest difference in sequence, was not important for the recognition of them but the N-terminal flexible portion was responsible for their opposite actions on the gallbladder. Tissue distribution of PACAP38, PACAP27, and PRP in guinea pigs was investigated by radioimmunoassay. Significant amounts of PACAP/PRP were present not only in the central nervous system but also in the gastrointestinal tract, where they were present in the enteric neurons. Several fragments of endothelin and secretin receptors were chemically synthesized and their specific antibodies were raised. On immunoblotts of pancreatic membranes subjected to SDS-polyacrylamide gel electrophoresis, antisera against secretin receptor fragments showed positive bands around 50kDa. Rat pancreatic ducts were strongly stained and acini with less degree by these antisera.

Report

(2 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (64 results)

All Other

All Publications (64 results)

  • [Publications] H Mifune,et al.: "Effects of enviromental temperature on atrial natriuretic peptide(ANP)-granules of auricular cardiocytes and plasma ANP level in pregnant rats" Exp.Animals.42. 243-247 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara,et al.: "Rapid synthesis and molecular mechanisms of substance K and its related peptides" Peptides 1992. 667-668 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara,et al.: "Synthesis and structure-activity relationship of PACAP-VIP related peptides" Peptides 1992. 723-724 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Muramoto,et al.: "Sensitization of gas-phase protein sequencer using fluorescein isothiocyanate(FITC)" Methods in protein sequence analysis. 29-36 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S Naruse,et al.: "Vasodilator effect of pituitary adenylate cyclase activating polypeptide(PACAP)on femoral blood flow in dogs" Peptides. 14. 505-510 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara,et al.: "Studies on D/L acids in solid phase peptide synthesis:synthetic conditions and racemization" Peptide Chemistry 1992. 103-106 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M Noda,et al.: "Development of novel acid-labile peptide amide linkers and their evaluation using a simultaneous peptide synthesizer" Peptide Chemistry 1992. 110-112 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] F.Herbst,et al.: "Development and applications of novel stationary phases for the HPLC separation of proteins and peptides(Part3),derivatized titaniumdioxide" Peptide Chemistry 1992. 204-207 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] V.Wray,et al.: "Solution structure of PACAP by ^1H NMR spectroscopy,distance geometry,and molecular dynamic calculations" Peptide Chemistry 1992. 220-223 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] V.Wray,et al.: "Solution structure of pituitary adenylate cyclase activating polypeptide be nuclear magnetic resonance spectroscopy" Biochemistry. 32. 5832-5841 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Muramoto,et al.: "Gas-phase microsequencing of peptides and proteins with a fluorecent edman-type reagent,fluorescein isothiocyanate" Biosci.Biotech,Biochem.58. 300-304 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y Yokomizo,et al.: "Efficient synthesis for phosphopeptides by the fmocstrategy" Peptide Chemistry 1993. 21-24 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara,et al.: "Rapid and efficient preparation for affinity columns,in which peptide as ligands bound to the solid-phase support" Peptide Chemistry 1993. 25-28 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara,et al.: "Highly efficient synthesis of PACAP and its related peptides and their biological actions in conscious dogs" Peptide Chemistry 1993. 265-268 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara,et al.: "Instrumentation for semi-large scale continuous-flow peptide synthesis with solvent and acyl component recovery systems" Peptides:Chemistry and Biology. 68-70 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Wei,et al.: "The effect of pituitary adenylate cyclase activation polypeptide(PACAP)38 on gallbladder smooth muscle in vitro" Biomed.Res.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S Naruse,et al.: "The effect of PACAP and VIP on isolated guinea pig pulmonary artery" Biomed.Res.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T Nakamura,et al.: "The effect of calcitonin gene-related peptide on gastrointestinal circulation in conscious dogs" Biomed.Res.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara,et al.: "Two-dimensional electrophoresis as a complementary method of isolating peptide fragments of cleaved proteins for internal sequencing" J.Chrom.676. 233-238 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara,et al.: "Semi-large scale continuous-flow peptide synthesis with solvent and acyl components recovery" Amer.Biotech.Laboratory. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara,et al.: "Highly efficient peptide-amide preparation using a simultaneous multiple-peptide synthesizer with two novel acid labile linkers" Peptides:Chemistry and Biology. 85-87 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] E Ando,et al.: "Development of pituitary adenylate cyclase activating polypeptide(PACAPs)specific radioimmunoassay systems and distribution of PACAP-like immunoreactivity in guinea pig tissues" Biochemical Peptides,Proteins & Nucleic Acids. 1. 45-49 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M Kitagawa,et al.: "The effect of pituitary adenylate cyclase activating polypeptide(PACAP)on amylase secretion from guinea pig pancreatic acini" Biochemical Peptides,Proteins & Nucleic Acids. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wray.V.,et al.: "Synthesis,biological action and solution structure of PACAP-related peptide" Biochemical Peptides,Proteins & Nucleic Acids. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H Mifune, et al.: "Effects of enviromental temperature on atrial natriuretic peptide (ANP)-granules of auricular cardiocytes and plasma ANP level in pregnant rats" Exp.Animals.42. 243-247 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara, et al.: "Rapid synthesis and molecular mechanisms of substance K and its related peptides" Peptides 1992. 667-668 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara, et al.: "Synthesis and structure-activity relationship of PACAP-VIP related peptides" Peptides 1992. 723-724 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Muramoto, et al.: "Sensitization of gas-phase protein sequencer using fluorescein isothiocyanate (FITC)" Methods in protein sequence analysis. 29-36 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S Naruse, et al.: "Vasodilator effect of pituitary adenylate cyclase activating polypeptide (PACAP) on femoral blood flow in dogs" Peptides. 14. 505-510 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara, et al.: "Studies on D/L acids in solid phase peptide synthesis : synthetic conditions and racemization" Peptide Chemistry 1992. 103-106 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara, et al.: "Rapid and efficient preparation for affinity columns, in which peptide as ligands bound to the solid-phase support" Peptide Chemistry 1993. 25-28 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara, et al.: "Highly efficient synthesis of PACAP and its related peptides and their biological actions in conscious dogs" Peptide Chemistry 1993. 265-268 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara, et al.: "Instrumentation for semi-large scale continuous-flow peptide synthesis with solvent and acyl component recovery systems" Peptides : Chemistry and Biology. 68-70 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara, et al.: "Highly efficient peptide-amide preparation using a simultaneous multiple-peptide synthesizer with two novel acid labile linkers" Peptides : Chemistry and Biology. 85-87 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Wei, et al.: "The effect of pituitary adenylate cyclase activation polypeptide (PACAP) 38 on gallbladder amooth muscle in vitro" Biomed.Res.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S Naruse, et al.: "The effect of PACAP and VIP on isolated guinea pig pulmonary artery" Biomed.Res.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M Noda, et al.: "Development of novel acid-labile peptide amide linkers and their evaluation using a simultaneous peptide synthesizer" Peptide Chemistry 1992. 110-112 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] F.Herbst, et al.: "Development and applications of novel stationary phases for the HPLC separation of proteins and peptides (Part 3), derivatized titaniumdioxide" Peptide Chemistry 1992. 204-207 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] V.Wray, et al.: "Solution structure of PACAP by ^1H NMR spectroscopy, distance geometry, and molecular dynamic calculations" Peptide Chemistry 1992. 220-223 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] V.Wray, et al.: "Solution structure of pituitary adenylate cyclase activating polypeptide be nuclear magnetic resonance spectroscopy" Biochemistry. 32. 5832-5841 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Muramoto, et al.: "Gas-phase microsequencing of peptides and proteins with a fluorecent edman-type reagent, fluorescein isothiocyanate" Biosci.Biotech.Biochem.58. 300-304 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Yokomizo, et al.: "Efficient synthesis for phosphopeptides by the fmoc-strategy" Peptide Chemistry 1993. 21-24 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T Nakamura, et al.: "The effect of calcitonin gene-related peptide on gastrointestinal circulation in conscious dogs" Biomed.Res.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara, et al.: "Two-dimensional electrophoresis as a complementary method of isolating peptide fragments of cleaved proteins for internal sequencing" J.Chrom.676. 233-238 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K Nokihara, et al.: "Semi-large scale continuous-flow peptide synthesis with solvent and acyl components recovery" Amer.Biotech.laboratory. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] E Ando, et al.: "Development of pituitary adenylate cyclase activating polypeptide (PACAPs) specific radioimmunoassay systems and distribution of PACAP-like immunoreactivity in guinea pig tissues" Biochemical peptides, Proteins & Nucleic Acids. 1. 45-49 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M Kitagawa, et al.: "The effect of pituitary adenylate cyclase activating polypeptide (PACAP) on amylase secretion from guinea pig pancreatic acini" Biochemical Peptides, Proteins & Nucleic Acids. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wray.V., et al.: "Synthesis, biological action and solution structure of PACAP-related peptide" Biochemical Peptides, Proteins & Nucleic Acids. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 成瀬 達: "食後の消化管粘膜における血流増加はなぜ起こるか." 医学のあゆみ. 156. 154-157 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 成瀬 達: "Pituitary adenylate cyclase activating polypeptide(PACAP)." 肝胆膵. 27. 969-975 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naruse S,Suzuki T,Ozaki T: "Vasodilator effect of pitutary adenylate cyclase activating polypeptides(PACAP)on femoral blood flow in dogs." Peptides. 14. 505-510 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Wray,V.,Kakoschke,C.,Nokihara K,Naruse S.: "Solution structure of pitutary adenylate cyclase activating polypeptide by nuclear magnetic resonance spectroscopy." Biochemistry. 32. 5832-5841 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naruse S,Sazi T,Ozaki T,Wray,V.Nokihara K: "The effect of PACAP and VIP on isolated guinea pig pulmonary artery." Biomed.Res.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Wei,M.S.,Naruse S,Nakayama T,Nokihara K,Ozaki T.: "The effect of pituitary adenylate cyclase activating polypeptide(PACAP)38 on gall-bladder smooth muscle in vitro." Biomed.Res.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Furuya S,Furuya K: "Characteristics of cultured subepithelial fibroblasts of rat villi" Anat Embryol. 187. 529-538 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakayama T,Naruse S,Wei,M.: "The effect of calcitonin gene-related peptide on gastrointestinal blood flow in conscious dogs." Biomed.Res.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 鈴木貴祐、成瀬達、矢内原昇: "「PACAPの酵素分泌刺激作用」 消化管ホルモンXII" 医学図書出版, 753 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 成瀬 達: "「食物摂取による血流の変化と胃運動」 第2回大雪シンポジウム 急性胃粘膜病変-その基礎と臨床" 医学図書出版, 203 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nokihara K,Naruse S,Ando E,Wray,V.: "「Synthesis and structure-activity relationship of PACAP-VIP related peptides」" Escom Science Publishers BV, 380 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Wray,V.,Nokihara K,Naruse S.: "「Solution structure of PACAP by ^1H NMR spectroscopy,distance geometry,and molecular dynamic calculations」" Escom Science Publishers BV, 380 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naruse S,Takagi T,Kato M,Ozaki T.: "「Relationship between gastric blood flow and motility」" Excerpta Medica, 180 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nokihara K,Naruse S,Ando E: "「Design,synthesis and biological actions of PACAP-related peptides based on structures from NMR studies」" World Scientific (in press), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nokihara K,Ando E,Naruse S,Nakamura T,Wray V: "Highly efficient synthesis of PACAP and its related peptidesand their biological actions in conscious dogs." Protein Research Foundation (in press), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naruse S,Nakamura T,Nokihara K,Ando E,Wray,V.: "「The effect of PACAP on gastrointestinal blood flow in conscious dogs」" World Scientific (in press), (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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