Study on superagonist and antagonist of brain-gut peptide

脑肠肽超级激动剂和拮抗剂的研究

• 批准号: 03454520
• 负责人: YANAIHARA Noboru
• 金额: $ 3.65万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454520/
• 关键词: 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

Studies on superagonist and antagonist of brain-gut peptideThe 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.

脑肠肽超激动剂和拮抗剂的研究本研究的目的是开发新的脑肠肽超激动剂和拮抗剂。1）甘丙肽的结构与功能研究表明，甘丙肽氨基端1-15序列是决定其活性的关键。为了开发甘丙肽拮抗剂，我们对几种新合成的甘丙肽类似物进行了研究。其中之一。[D-Thr^6，D-Trp^8，9>]甘丙肽（1-15）-醇在体外对葡萄糖诱导的胰岛素释放具有拮抗作用。2）完成了由69个氨基酸残基组成的人甘丙肽的全合成。此外，胰高血糖素相关肽的结构-功能研究表明，胰高血糖素样肽（GLP）1（7-33）以及GLP-1（7-37）和GLP-1（7-36）酰胺均具有较强的促胰岛素活性，提示GLP-1的主要活性位点位于7-33序列。3）利用新发现的PACAP拮抗剂PACAP（5-38）等PACAP C端片段，4）设计PTHrP（7-34）类似物[desamino-Leu^8，Asn^<10>，Leu^<11>，D-Trp^<12>]PTHrP（8-34）NH_2在体内外均为PTHrP拮抗剂。该检测系统可用于脑肠肽的研究。

项目成果

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)

M.渡边，N.

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)

H.Asai、N.Yanaihara 等人：“衰老豚鼠呼吸道中 P 物质和血管活性肠多肽水平的变化”Biomed.Res.12。

Min Li,Noboru Yanaihara: "Helodermin analogues:structure-function studies of helodermin" Biomed.Res.14(3). 61-69 (1993)

李敏，柳原升：“毒蜥皮素类似物：毒蜥皮素的结构功能研究”Biomed.Res.14(3)。

N.Yanaihara,et al.: "Structureーfunction relationships of galanin" Galanin:Macmillan Education Ltd.185-196 (1991)

N. Yanaihara 等人：“甘丙肽的结构-功能关系” 甘丙肽：Macmillan Education Ltd. 185-196 (1991)

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)

Yoshio Murakami，Noboru Yanaihara：“人甘丙肽对正常男性生长激素、催乳素和抗利尿激素分泌的影响”J.临床内分泌与代谢。