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Studies on structure-activity relationship and intracellular signal transduction systems of neuropeptides

神经肽构效关系及细胞内信号转导系统研究

基本信息

批准号：
61304043
负责人：
KITO Shozo
金额：
$ 19.2万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

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 … More 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

1.从形态学和药理学两方面研究了神经肽在中枢神经系统中的分布、功能机制及其与经典神经递质的相互作用。特别强调了生长抑素和毒蕈碱乙酰胆碱受体之间的相互作用，在大鼠海马和纹状体（Kito）的各种神经递质之间的突触形成的证据的电子显微镜研究。2.从结构鉴定、构效关系和药理机制等方面对马蜂毒素进行了研究。3.对神经肽如神经激肽A、B和内皮素等由金泽及其同事发现的神经肽的生理功能进行了研究（金泽）。4.甘丙肽和GLP-I是新发现的神经肽，对它们的分布、功能和构效关系进行了研究（Yanaihara）。5. P物质和神经激肽A， ...更多信息脊髓背角初级传入神经元中的ned被证实引起对伤害性刺激的慢EPSP，从而在疼痛传导中起作用（Otsuka）。6.用GH_3细胞证实了TRH受体的细胞表面定位和内化。此外，已知TRH受体和VIP受体在彼此不同的第二信使系统水平上相互作用（Ogawa）。7.对kyotorphin的研究已发展到脑内特异性受体的鉴定、细胞内信号转导系统和生物合成途径。还发现CGRP参与持续性疼痛（Sato）。8.用原位杂交技术观察了脊髓和后根神经节内P物质和脑啡肽的基因表达，并探讨了它们在伤害性刺激中的功能意义。对各种神经肽的分布和共存进行了广泛的化学研究（Tohyama）。9.在正常大鼠上分析了生长抑素和神经thensin受体的分布和信号转导机制，并将这些研究扩展到惊厥模型动物（Saitoh）。10.研究了肝脏循环系统中血管作用神经肽的分布（化学分析），并在肝脏疾病中证实了这些肽的血清浓度异常（Kamada）。11.对心房利钠肽和脑利钠肽的结构、分布和作用机制进行了比较研究（Matsuo）。少