权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of new mastoparan-related peptides which stimulate or inhibit the secretory activity of cells

开发刺激或抑制细胞分泌活性的新型乳腺相关肽

基本信息

批准号：
07558234
负责人：
KASAI Hisataka
金额：
$ 2.18万
依托单位：
Tokyo Metropolitan University of Health Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

This study aimed to develop new mastoparan (MP)-related peptides which stimulate or inhibit the secretory activity of cells such as adrenal chromaffin cells and mast cells. We designed and synthesized 7 MP fragments including N-terminal four residues (INLK-NH_s ; N-4) and C-terminal four residues (KKIL-NH_2 ; C-4) and their several analogs (13 species).We examined their effect of some biological activities of MP.Results were as follows.(1) All the synthesized peptides in this study had no catecholamine (CA) releasing activity, activity of GTP ase activation or hemolytic activity.(2) N-4 and C-4 fragments both inhibited MP-and acetylcholine (ACh)-stimulated CA-release from chromaffin cells with a bath application system. From the inhibitory effect on some kinds of agonists-stimulated CA-release, it is concluded that N-4 and C-4 fragments selectively inhibit the nicotinic secretory response by attacking the nicotinic ACh receptors (nAChR) on the site (s) other than ACh binding site.(3) From the structure and function-releationship of N-4 analogs, the site (s) on nAChR attacked by N-4 are suggested to be made of hydrophobic amino acids and acidic amino acids. One of the analogs was about five times as strong as N-4 in nAChR inhibitory activity.(4) MP-stimulated GTP ase activity was inhibited by C-4 but not by N-4.therefore, CA release evoked by MP from chromaffin cells is supposed to be mediated by an unknown exocytotic process.As the next process of this work, we will approach to a possibly of these newly synthesized peptides to act effectively on several certain disease.

本研究的目的是开发新的mastoparan（MP）相关肽，刺激或抑制细胞，如肾上腺嗜铬细胞和肥大细胞的分泌活性。我们设计合成了包括N端4个残基（INLK-NH_3; N-4）和C端4个残基（KKIL-NH_2 ; C-4）在内的7个MP片段及其13种类似物，研究了它们对MP生物活性的影响。(1)本研究所合成的多肽均无儿茶酚胺释放活性、GTP酶激活活性和溶血活性。(2)N-4和C-4片段均能抑制MP和乙酰胆碱（ACh）刺激的嗜铬细胞CA释放。从对几种激动剂刺激的CA释放的抑制作用来看，N-4和C-4片段选择性地抑制烟碱分泌反应是通过攻击烟碱型ACh受体（nAChR）上的非ACh结合位点。(3)根据N-4类似物的结构和功能关系，推测N-4攻击nAChR的位点是由疏水氨基酸和酸性氨基酸组成的。其中一种类似物的nAChR抑制活性约为N-4的5倍。(4)MP刺激的GTP酶活性可被C-4抑制，而不被N-4抑制，因此，MP诱导的嗜铬细胞CA释放可能是通过一个未知的胞吐过程介导的。