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Study on superagonist and antagonist of brain-gut peptide

Research Project

Project/Area Number 03454520
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionUniversity of Shizuoka

Principal Investigator

YANAIHARA Noboru  Univ.of Shizuoka, School of Pharm.Sciences, Professor, 薬学部, 教授 (80046250)

Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1992: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1991: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsgalanin / glicentin / PACAP / PTHrP / chromogranin / superagonist / antagonist / chemical synthesis / クロモグラニンA / ヘロデルミン / ヒト・グリセンチン / [D-Thr^6,D-Trp^<8,9>]galanin(1-15)-ol / ヒト神経芽細胞腫培養細胞系NB-OK-1 / 脳腸ホルモン / アゴニスト / 特異抗体
Research Abstract

Studies on superagonist and antagonist of brain-gut peptide
The aim of the present study was to develop newly designed super agonist and antagonist of brain-gut peptide.
1) Structure-function studies on galanin reveled that the galanin amin-terminal 1-15 sequence is crucial for its activity in several bioassay system. In order to develop galanin antagonist, we have examined several galanin analogs, which were newly synthesiged. Among them.[D-Thr^6, D-Trp^<8,9>]galanin(1-15)-ol was found to act as a galanin antogonist on glucose-induced insulin release in vitro.
2) Total synthesis of human glicentin comprising 69 amino acid residues was completed. In addition, structure-function studies on glucagon-related peptides revealed that glucagon-like peptide(GLP)1(7-33)as well as GLP-1(7-37) and GLP-1(7-36)amide showed potent insulinotropic activity, suggesting that major active site of GLP-1 resides in the 7-33 sequence.
3) Using PACAP C-terminal fragment such as PACAP(5-38), which is newly discovered PACAP antagonist, PACAP receptor and helodermin-affinity receptor were clearly characterized.
4) Purposely designed PTHrP(7-34)analog such as[desamino-Leu^8, Asn^<10>, Leu^<11>, D-Trp^<12>]PTHrP(8-34)NH_2 was found to be a potent PTHrP antagonist in vitro and in vivo.
5) Radioimmunoassay specific for chromogranin A was developed. This assay system was shown to be useful for brain-gut peptide research.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Noboru Yanaihara: "Galanin analogues:agonist and antagonist" Regul.Pept.46. 93-101 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Hoshino,N.Yanaihara: "Pituitary adenylate cyclase activating peptide and vasoactive intestinal polypeptide:differentiation effects on human neuroblastoma NB-OK-1 cells" Neurosci.Lett.159. 35-38 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Min Li,Noboru Yanaihara: "Helodermin analogues:structure-function studies of helodermin" Biomed.Res.14(3). 61-69 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yoshio Murakami,Noboru Yanaihara: "Effect of human galanin on growth hormone,prolactin,and antidiuretic hormone secretion in normal men" J.Clinical Endocrinology and Metabolism. 77(5). 1436-1438 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] David Wynick,Noboru Yanaihara: "Characterization of a High-affinity galanin receptor in the rat anterior pituitary:Absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor." Proc.Natl.Acad.Sci.USA.90. 4231-4235 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 長沢晋吾、矢内原昇: "ラット下垂体、視床下部および膵におけるクロモグラニンAのブロセッシングの比較" 消化管ホルモン. (XII). 346-356 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tohru Mochizuki,Noboru Yanaihara: "Peptide Chemistry 1992" ESCOM Science Publishers B.V., 4 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Keiichi Ohshima,Noboru Yanaihara: "Peptide Chemistry 1992" ESCOM Science Publishers B.V., 3 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Noboru Yanaihara: "Galanin analogues:agonist and antagonist" Regul.Pept.46. 93-101 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Hoshino,N.Yanaihara: "Pituitary adenylate cyclase activating peptide and vasoactive intestinal polypeptide:differentiation effects on human neuroblastoma NB-OK-1 cells21GC02:Neurosci.Lett." 159. 35-38 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Min Li,Noboru Yanaihara: "Helodermin analogues:structure-function studies of helodermin" Biomed.Res.14(3). 61-69 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshio Murakami,Noboru Yanaihara: "Effect of human galanin on growth hormone,prolaction,and antidiuretic hormone secretion in normal men" J.Clinical Endocrinology and Metabolism. 77(5). 1436-1438 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] David wynick,Noboru Yanaihara: "Characterization of a High-affinity galanin receptor in the rat anterior pituitary:Absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor." Proc.Natl.Acad.Sci.USA.90. 4231-4235 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 長沢晋吾、矢内原昇: "ラット下垂体、視床下部および膵におけるクロモグラニンAのプロセッシングの比較" 消化管ホルモン. (XII). 346-356 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tohru Mochizuki,Noboru Yanaihara: "Peptide Chemistry 1992" ESCOM Science Publishers B.V., 4 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Keiichi Ohshima,Noboru Yanaihara: "Peptide Chemistry 1992" ESCOM Science Publishers B.V., 3 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y. Ishizuka ,N.Yanaihara: "Cardiovascular and respiratory actions of pituitary adebylate cyclase-activating polypeptides" Regulatory Peptides. 40. 29-39 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S. Naruse ,N. Yanaihara: "Vasodilator action of guinea pig vasoactive intestinal polypeptide(VIP):comparison with common mammalian VIP" Regulatory Peptides. 42. 163-171 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T. Mochizuki ,N. Yanaihara: "Effects of galanin fragments on insulin release from the isolated perfused rat pancreas" Biomedical Research. 13(3). 203-213 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S. Sumi ,N. Yanaihara: "Stractural requirements of peptide YY for biological activity at enteric sites" The American Physiological Society. 263. G695-G701 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] P. B. Hedlund,N. Yanaihara: "Evidence for specific N-terminal galanin fragment binding sites in the rat brain" European Journal of Pharmacology. 224. 203-205 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M. Watanabe,N. Yanaihara: "Localization of gastrin-releasing peptide(GRP)-like immunoreactivity in the lysosomal compartment of the trigeminal ganglion cells of the rat" Histochemistry. 97. 277-281 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] YーJ.Jeng,N.Yanaihara,et al.: "Regulation of pancreastatin release from a human pancreatic carcinoid cell line in vitro" Endocrinology. 128. 220-225 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Sasaki,N.Yanaihara,et al.: "Effects of fibroblast growth factors and plateletーderived growth factor on food intake in rats" Brain Research Bulletin. 27. 327-332 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] N.Nakayama,N.Yanaihara,et al.: "Effects of porcine galanin on the mesenteric microcirculation and arteriolar smooth muscle in the rat" European Journal of Pharmacology. 193. 75-80 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Tsuruo,N.Yanaihara,et al.: "Substance Pーcontaining neurons innervating LHRHーcontaining neurons in the septoーpreoptic area of rats" Neuroendocrinology. 53. 236-245 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Tanoh,N.Yanaihara,et al.: "Cholinergic modulation of growth hormone secretion induced by galanin in rats" Neuroendocrinology. 54. 83-88 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] H.Asai,N.Yanaihara,et al.: "Changes in substance P and vasoactive intestinal polypeptide levels in the respiratory tract of aging guinea pigs" Biomed.Res.12. 41-46 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Nakamura,N.Yanaihara,et al.: "Comparison of in vivo biological activities of luteinizing hormone releasing hormone(LHRH)analogues in 60ーdayーold cockerels" General and Comparative Endocrinology. 83. 290-296 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] N.Yanaihara(ed.K.Shimuzu): "Regulatory peptides and proteinsーpresent and future topics" Now & Future Japan Industrial Technology Asociation,Tokyo. 2-4 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] N.Yanaihara,et al.: "Structureーfunction relationships of galanin" Galanin:Macmillan Education Ltd.185-196 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Ohshima,N.Yanaihara,et al.(ed.Y.Shimonishi): "Synthesis of porcine gastric inhibitory polypeptide(GIP)(1ー30)and its biological activity" Peptide Chemistry 1990 Protein Research Foundation,Osaka. 255-260 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Mochizuki,N.Yanaihara,et al.(ed.Y.Shimonishi): "Structureーfunction relationship of galanin" Peptide Chemistry 1990 Protein Research Foundation,Osaka. 373-378 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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