1988 Fiscal Year Final Research Report Summary
Studies on structure-activity relationship and intracellular signal transduction systems of neuropeptides
| Project/Area Number |
61304043
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KITO Shozo Hiroshima University School of Medicine, Prof., 医学部, 教授 (00010140)
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| Co-Investigator(Kenkyū-buntansha) |
TOHYAMA Masaya Osaka University Medical School, Prof., 医学部, 教授 (40028593)
SATOH Masamichi Faculty of Pharmaceutical Sciences, Kyoto University, Prof., 薬学部, 教授 (80025709)
OTSUKA Masanori Faculty of Medicine, Tokyo Medical and Dental University, Prof., 医学部, 教授 (60013801)
YANAIHARA Noboru Laboratory of Bioorganic Chemistry, Shizuoka College of Pharmacy, Prof., 薬学部, 教授 (80046250)
NAKAJIMA Terumi Faculty of Pharmaceutical Science, University of Tokyo, Prof., 薬学部, 教授 (50012597)
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| Project Period (FY) |
1986 – 1988
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| Keywords | Somatostatin / Mastoparan / Galanin / TRH / Kyotorphin / Tachykinin / Natriuretic polypeptide / 作用機序 |
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| Research Abstract |
1. Morphological and pharmacological investigations were done on the distribution and functional mechanisms of neuropeptides in the central nervous system, and their interactions with classical neurotransmitters. Particular emphasis was put on interactions between somatostatin and muscarinic acetylcholine receptors in the rat hippocampus, and electron microscopic studies on evidence of synaptic formations among vaious neurotransmitters in the striatum (Kito). 2. Mastoparan, a peptide toxin from wasp venom, was studied from viewpoints of structure identity, structure-activity relationship and pharmacological mechanism (Nakajima). 3. Neuropeptides such as neurokinin A, B and endothelin which were discovered by Kanazawa and his associates were studied on their physiological functions (Kanazawa). 4. Galanin and GLP-I, newly discovered neuropeptides, were investigated on distribution, function and structure-activity relationship (Yanaihara). 5. Substance P and neurokinin A which were contai
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ned in the primary afferent neurons in the spinal dorsal horn were confirmed to cause slow EPSP on nociceptive stimulations, thus playing a role on pain conductions (Otsuka). 6. Using GH_3 cells, cell surface localization and internalization of TRH receptors were verified. Besides, TRH receptors and VIP receptors were known to be interacted at the level of second messenger systems which were different each other (Ogawa). 7. Studies on kyotorphin have progressed up to identification of intracerebral specific receptor, the intracellular singnal transduction system and biosynthetic pathways. Participation of CGRP on persisting pain was also found out (Sato). 8. By means of in situ hybridization, gene expression of substance P and enkephalin in the spinal cord and posterior root ganglia was observed and functional significance of these peptides on nociceptive stimulations were discussed. Distribution and coexistence of various neuropeptides were immunohistochemically extensively studied (Tohyama). 9. Distributions and signal transduction mechanisms of somatostatin and neurothensin receptors were analysed on normal rats and these studies were extended to model animals of convulsion (Saitoh). 10. Distributions of vasoacting neuropeptides in the hepatic circulation system were studied (immunohistochemically and abnormalities of serum concentrations of these peptides were confirmed in hepatic disorders (Kamada). 11. Comparative studies on structure, distribution and functional mechanism between atrial natriuretic peptide and brain natriuretic peptide were performed (Matsuo). Less
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