| Project/Area Number |
07558234
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Metropolitan University of Health Sciences |
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Principal Investigator |
KASAI Hisataka Tokyo Metropolitan University of Health Sciences, School of Physical Therapy/Professor, 一般教養科, 教授 (80087163)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUCHI Akira Mitui Seiyaku Industry Co., Research Project Team/Head Researcher, 新薬計画部, 主席部員
KUMAKURA Konosuke Sophia University, Faculty of Science and Technology/Professor, 理工学部, 教授 (70129790)
ITO Hisashi Aoyama Gakuin University, Department of Chemistry/Professor, 理工学部, 教授 (70082815)
TATEYAMA Masato Tokyo Metropolitan University of Health Sciences, School of Occupational Therapy, 作業療法学科, 教授 (60118966)
SUDA Haruhiko Tokyo Metropolitan University of Health Sciences, School of Occupational Therapy, 作業療法学科, 教授 (40051784)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Mastoparan / Exocytosis / Catecholamine / Histamine / Nicotinic acetylcholine receptor / GTP ase activity / Chromaffin cell / Mast cell / マストパラン / カデコールアミン / アセチルコリン / ニコチン性レセプター / GTPアーゼ / アストパラン / Gタンパク質 |
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| Research Abstract |
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.
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