Search for novel hormones and neuropeptides

寻找新的激素和神经肽

• 批准号: 04404084
• 负责人: TATEMOTO Kazuhiko
• 金额: $ 18.56万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04404084/
• 关键词: biologically active peptide; hormone; neuropeptide; growth factor; differentiation-inducing factor; peptide isolation; peptide structure; 生理活性; ペプチド

The principal aim of this proposal is to isolate novel hormones and neuropeptides using a variety of assay methods and to characterize physiological and biochemical properties of the peptides. Toward this goal, we first set up a new laboratory which is capable of carrying out peptide isolation, structural determination, chemical synthesis and various physiological and pharmacological studies, then, we carried out isolation studies and various physiological studies. In this study, we isolated and characterized that : 1)novel antimicrobial peptides, rugosins, A,B,and C from the skin of the frog, rana rugosa ; 2)a novel CCK-releasing peptide from porcine intestine ; 3)insulin-like growth factor (IGF)-II and IGF binding protein-2 from brain meningeal cells ; 4)novel motilin-related peptides from porcine intestine. We also found that : 1)meninges play a neurotrophic role in the regeneration of vasopressin nerves after hypophysectomy ; 2)biotinyl C-terminal-extended motilin can be used as a biologically active receptor probe ; 3)differentiation-inducing factor (DIF-1) raises intracellular calcium concentration and induces apoptosis in pancreatic AR42J cells ; 4)pancreastatin inhibits secretagogues-induced rise in intracellular free calcium in single rat pancreatic islet cells ; 5)GLP-1 depolarizes rat pancreatic B-cells in a Na+dependent manner ; 6)bradykinin rises the intracellular calcium concentration of pancreatic acinar AR42J cells.

该提案的主要目的是使用各种测定方法分离新的激素和神经肽，并表征肽的生理和生化特性。为了实现这一目标，我们首先建立了一个新的实验室，能够进行肽分离，结构测定，化学合成和各种生理和药理学研究，然后，我们进行了分离研究和各种生理研究。本研究中，我们分离并鉴定了：1）从皱纹蛙皮肤中分离得到的新型抗菌肽Rugosins A、B和C; 2）从猪肠中分离得到的新型CCK释放肽; 3）从脑膜细胞中分离得到的胰岛素样生长因子（IGF）-II和IGF结合蛋白-2; 4）从猪肠中分离得到的新型胃动素相关肽。我们还发现：1）脑膜在垂体切除后加压素神经再生中起神经营养作用，2）生物素C末端延伸的胃动素可作为生物活性受体探针，3）分化诱导因子（DIF-1）可升高胰腺AR 42 J细胞内钙离子浓度并诱导其凋亡; 4）胰蛋白酶抑制剂抑制单个大鼠胰岛细胞中促分泌素诱导的细胞内游离钙升高; 5）GLP-1以Na+依赖性方式使大鼠胰腺B细胞去极化; 6）缓激肽升高胰腺腺泡AR 42 J细胞内钙离子浓度。

项目成果

Saito,Y.,Kato,M.,Kubohara,Y.,Kobayashi,I,Tatemoto,K.: "Bradykinin increases intracellular free Ca+ concentration and promotes insulin secretion in the clonal B-cell line,HIT-15 cells." Biochem.Biophys.Res.Commun.(in press.).

Saito,Y.、Kato,M.、Kubohara,Y.、Kobayashi,I、Tatemoto,K.：“缓激肽可增加细胞内游离 Ca 浓度并促进克隆 B 细胞系 HIT-15 细胞中的胰岛素分泌。”

立元一彦、馬 洪涛、加藤昌克: "パンクレアスタチン:膵内外分泌を調節する局所ホルモン" 臨床消化器内科. 10 (7). 929-936 (1995)

Kazuhiko Tatemoto、Hongtao Ma、Masakatsu Kato：“胰腺素：调节胰腺内外分泌的局部激素”临床胃肠病学 10 (7) (1995)。

Ishikawa K., Ohe Y., Tatemoto K.: "Synthesis and secretion of insulin-like growth factor (IGF) -II and IGF binding protein-2 by cultivated brain meningeal cells." Brain Research. 697. 122-129 (1995)

Ishikawa K.、Ohe Y.、Tatemoto K.：“培养的脑膜细胞合成和分泌胰岛素样生长因子 (IGF)-II 和 IGF 结合蛋白-2。”

Ma,H-T.,Kato,M.,Tatemoto,K.: "Effects of pancreatatin and somatostatin on secretagogues-induced rise in intracellular free calcium in single rat pancreatic islet cells." Regulatory Peptides. (in press.).

Ma，H-T.，Kato，M.，Tatemoto，K.：“胰酶和生长抑素对促分泌素诱导的单个大鼠胰岛细胞中细胞内游离钙升高的影响。”

立元一彦: "消化管ホルモン研究の親展開-化学構造と分類" 胆と膵. 15. 815-821 (1994)

Kazuhiko Tatemoto：“胃肠激素研究的进展 - 化学结构和分类”胆汁和胰腺 15。815-821（1994）。