| Project/Area Number |
03454520
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | University of Shizuoka |
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Principal Investigator |
YANAIHARA Noboru Univ.of Shizuoka, School of Pharm.Sciences, Professor, 薬学部, 教授 (80046250)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| 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)
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| Keywords | galanin / 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 |
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| 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.
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