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SEARCH FOR NOVEL GASTROINTESTINAL HORMONES

寻找新型胃肠激素

基本信息

批准号：
3238942
负责人：
GARY M. GRAY
金额：
$ 31.17万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-09-01 至 1994-02-28
项目状态：
已结题

项目摘要

The principal aim of this proposal is to isolate novel neuro- and hormonal peptides from the gut and pancreas using a variety of the detection methods and subsequently characterize the chemical, biological and immunochemical properties of the isolated peptides. Large-scale extractions of the tissue materials will be followed by purification using gel permeation, ion exchange and high performance liquid chromatography (HPLC). Specifically, the following gut peptides will be screened: 1) novel peptides which possess the C-terminal amide structure using a chemical assay method; 2) novel peptide which contract or relax smooth muscles using smooth muscle preparations; 3) endogenous gut factors which alter the release of the hormones from pituitary, hypothalamic and intestinal cell cultures. The primary structure of the isolated peptides will be determined using automatic gas-phase sequencing, amino acid analysis and fast- atom-bombardment (FAB) mass spectrometry. Synthetic replicates of the peptides will be prepared using solid-phase synthesizers and will be utilized for generating antibodies, and for pharmacological studies. Further, peptide analogues of peptide YY and neuropeptide Y that have agonist and antagonist activities will be synthesized using a multiple solid-phase peptide synthesis technique. Antibodies raised against the peptides will be used for cellular localization studies using radioimmunoassay and immunohistochemical methods. The structure of precursors of the peptides will be determined by gene cloning techniques and oligonucleotide probes will be utilized for studies of mRNA levels in tissues and for in situ hybridization studies. This study is likely to find a host of new neuropeptides and hormones which have important biological significance and stimulate various physiological, pharmacological, biochemical, and clinical studies. We anticipate that such studies will shed further light on the regulatory mechanisms of the digestive system and will have implications toward understanding the pathogenesis of some digestive diseases.

这项提议的主要目的是分离新的神经细胞和肠道和胰腺中的荷尔蒙多肽使用各种检测方法，并随后描述牛血清白蛋白的化学、生物学和免疫化学性质分离的多肽。组织材料的大规模提取之后将使用凝胶渗透纯化，离子交换和高效液相色谱(HPLC)。具体地说，将筛选出以下肠肽：1)新颖具有C-末端酰胺结构的多肽使用化学测定法；2)收缩或松弛的新肽使用平滑肌制剂的平滑肌肉；3)内源性改变荷尔蒙释放的肠道因素脑垂体、下丘脑和肠道细胞培养。初级阶段分离的多肽的结构将用自动气相测序，氨基酸分析和快速- 原子轰击(FAB)质谱仪。合成的将使用固相法制备肽的复制品合成器，将被用来产生抗体，并用于药理学研究。此外，多肽的多肽类似物具有激动剂和拮抗剂活性的YY和神经肽Y 将采用多固相合成法合成多肽技术。针对这些多肽产生的抗体将用于放射免疫分析和细胞定位研究免疫组织化学方法。前驱体的结构这些多肽将通过基因克隆技术和将使用寡核苷酸探针来研究mRNA水平用于组织和原位杂交研究。这项研究可能会发现一系列新的神经肽和具有重要生物学意义的激素和刺激各种生理，药理，生化，和临床研究。我们预计这样的研究将不会进一步阐明消化系统的调节机制系统，并将对理解一些消化系统疾病的发病机制。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Synthesis of receptor antagonists of neuropeptide Y.

神经肽Y受体拮抗剂的合成。

DOI：
10.1073/pnas.89.4.1174
发表时间：
1992
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Tatemoto,K;Mann,MJ;Shimizu,M
通讯作者：
Shimizu,M

Intracranial microinfusion of pancreastatin elevates blood glucose, free fatty acids, and corticosterone in rats.

颅内微量胰酶输注可升高大鼠的血糖、游离脂肪酸和皮质酮。