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STUDIES ON SIGMA RECEPTORS AND THEIR LIGANDS

西格玛受体及其配体的研究

基本信息

批准号：
3378352
负责人：
ECKARD WEBER
金额：
$ 14.45万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-04-01 至 1994-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3378352
关键词：
active sites affinity chromatography affinity labeling antipsychotic agents guinea pigs high performance liquid chromatography liver neuropeptide receptor opioid receptor protein purification protein sequence protein structure function receptor binding reversed phase chromatography

项目摘要

DESCRIPTION (Adapted from the Applicant's Abstract): Sigma receptors are high affinity binding sites for haloperidol and other antipsychotic drugs. Because a number of atypical antipsychotic agents have been found to have a high affinity for sigma receptors, it has been proposed that sigma receptors may represent a common site of action for novel antipsychotic drugs which do not produce extrapyramidal side-effects. Other investigators, however, have proposed that sigma receptors mediate the motor side-effects of dopaminergic antipsychotic agents. Because sigma receptors are the major binding sites for many clinically useful psychopharmacological agents, it may be essential to elucidate their structure and function. A 29kD polypeptide, that has been identified as the binding subunit of the sigma receptor with the photoaffinity label \H|-azido-DTG, has now been isolated by SDS-electrophoresis and reversed phase HPLC. This polypeptide has been isolated from the solubilized guinea pig liver membrane, which contains a very high concentration of sigma receptors. This proposal will attempt to perform extensive amino acid sequence analysis on the isolated protein. Furthermore, additional protein(s) that may be part of the sigma receptor complex will be isolated by affinity chromatography using several newly developed affinity chromatography matrices. This work will provide a means to structurally characterize the sigma receptor binding subunit and/or additional proteins of the sigma receptor complex. Structural characterization of the sigma receptor should result in an elucidation of the function of this protein, and, therefore, may lead to a greater understanding of the functional consequences of the binding of psychopharmacological agents to sigma receptors in the brain and other tissues.

描述（改编自申请人的摘要）：氟哌啶醇和其他抗精神病药物的高亲和力结合位点。因为一些非典型抗精神病药物已被发现有一个对σ受体具有高亲和力，已经提出σ 受体可能是新型抗精神病药的共同作用部位不产生锥体外系副作用的药物。其他然而，研究者提出σ受体介导了多巴胺能抗精神病药物的运动副作用。因为sigma 受体是许多临床上有用的精神药理学药物，这可能是必要的，以阐明其结构和功能。一种29 kD多肽，已被鉴定为具有光亲和标记的σ受体的结合亚基 \H|- 叠氮基-DTG，现已通过SDS-电泳分离并逆转录相HPLC。这种多肽已从溶解的豚鼠中分离出来，猪肝膜，其含有非常高浓度的西格玛受体。该提案将尝试执行广泛的氨基酸对分离的蛋白质进行序列分析。此外，额外分离可能是σ受体复合物一部分的蛋白质通过使用几种新开发的亲和色谱法，色谱基质。这项工作将提供一种手段，表征σ受体结合亚基和/或另外的蛋白质 sigma受体复合物的一部分 sigma的结构表征受体的研究将有助于阐明这种蛋白质的功能，因此，可能会导致对功能的更好理解精神药物与西格玛结合的后果大脑和其他组织中的受体。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Distribution pattern of metorphamide compared with other opioid peptides from proenkephalin and prodynorphin in the bovine brain.

美吗啡酰胺与来自脑啡肽原和强啡肽的其他阿片肽在牛脑中的分布模式比较。

DOI：
10.1111/j.1471-4159.1987.tb00946.x
发表时间：
1987
期刊：
Journal of neurochemistry
影响因子：
4.7
作者：
Sonders,M;Weber,E
通讯作者：
Weber,E

Isolation and structure of a C-terminally amidated nonopioid peptide, amidorphin-(8-26), from bovine striatum: a major product of proenkephalin in brain but not in adrenal medulla.

来自牛纹状体的 C 末端酰胺化非阿片肽，amidophin-(8-26) 的分离和结构：脑啡肽原在大脑中的主要产物，但在肾上腺髓质中则不然。

DOI：
10.1073/pnas.83.6.1936
发表时间：
1986
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Liebisch,DC;Weber,E;Kosicka,B;Gramsch,C;Herz,A;Seizinger,BR
通讯作者：
Seizinger,BR

1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs.

DOI：
10.1073/pnas.83.22.8784
发表时间：
1986-11
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
E. Weber;M. Sonders;M. Quarum;S. Mclean;S. Pou;J. Keana
通讯作者：
E. Weber;M. Sonders;M. Quarum;S. Mclean;S. Pou;J. Keana

Immunohistochemical evidence for subpopulations of dynorphinergic neurons.

强啡能神经元亚群的免疫组织化学证据。