A Study of the Mitogenic Effects of Serotonergic Receptors

血清素受体促有丝分裂作用的研究

• 批准号: 7334769
• 负责人: BRADFORD A JAMESON
• 金额: $ 29.26万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7334769
• 关键词: 8-Hydroxy-2-(di-n-propylamino)tetralin; Accounting; Activated Lymphocyte; Address; Affect; Agonist; Animals; Antibodies; Antigen-Presenting Cells; Autoimmune Diseases; Back; Bacteria; Binding Sites; Biological Models; CD4 Positive T Lymphocytes; Cell Communication; Cell Culture System; Cell Line; Cells; Chimeric Proteins; Cloning; Complex; Confusion; Data; Doctor of Philosophy; Emotional; Ensure; Ergot Alkaloids; Generations; Graft Rejection; Growth; Growth Factor; Helper-Inducer T-Lymphocyte; Human; Immune response; Immune system; Knowledge; Lead; Literature; Lymphocyte; Messenger RNA; Nature; Neoplastic Lymphocyte; Neurotransmitters; Pathway interactions; Personal Satisfaction; Phenotype; Plants; Polymerase Chain Reaction; Population; Process; Proteins; Publishing; RNA Splicing; Race; Receptor Inhibition; Regulation; Reporting; Research Personnel; Role; Serotonin; Serotonin Receptor 5-HT1A; Signal Transduction; Signal Transduction Pathway; Small Interfering RNA; Source; Synaptic Transmission; System; T-Cell Proliferation; T-Lymphocyte; Techniques; Transcript; Tryptophan; Tryptophan 5-monooxygenase; Vertebrates; autocrine; base; cell growth; cell type; cytokine; design; immunological synapse; inhibitor/antagonist; knock-down; novel; novel therapeutics; prevent; programs; receptor; research study; response; serotonin receptor

Serotonin and its 14 cognate receptors have been well-characterized over the years, yet the data produces a confusing picture regarding their functionality. To large extent, the functional attributes of the receptors apparently depend upon the specific cell type in which they are expressed. This study is designed to characterize the role of serotonin and several different responding receptors in the stimulation and regulation of lymphocytes. Our preliminary data has established the presence of serotonin in this system and show that the receptors are functionally active. Pharmacological anomalies with the 5-HT 1A receptor have led us to the discovery of a novel chimeric mRNA that encodes a putative fusion protein containing the first third of the 1A protein. Based on our preliminary data three specific aims are proposed that are designed to fundamentally characterize the serotonin pathways in lymphocytes. The first aim is intended to explore whether serotonin is an autocrine survival factor in neoplastic lymphocytes and to expand our knowledge of the role of serotonin in the activation and differentiation of primary naive helper T cells. The second aim of the proposal is intended to functionally characterize the novel 1A-fusion transcript identified in the lymphocytes. The last aim of the proposal is designed to address the mechanism of action of the serotonergic signals that are transduced through its cognate receptors. For this aim, we will dissect the relevant signal transduction pathways associated with the 5-HT 1B receptor in a T cell line and in primary T cells. Basically, this proposal is designed to explore the role of serotonin (a neurotransmitter, well-known for its involvement in the control of emotional responses) in mounting immune responses. We hypothesize that serotonin is a critical regulator of the immune system. Understanding the nature and role of the serotonergic receptors in the immune system may lead to the advent of new therapeutic strategies to combat autoimmune disease and treat the problems associated with transplant rejection.

多年来，5-羟色胺及其14个同源受体已得到很好的表征，但是数据 就其功能产生令人困惑的图片。在很大程度上，功能属性 受体显然取决于表达的特定细胞类型。这项研究是设计的 表征5-羟色胺和几种不同反应受体在刺激中的作用 调节淋巴细胞。我们的初步数据已经在该系统中确定了5-羟色胺 并表明受体在功能上是活跃的。 5-HT 1A受体的药理异常 导致我们发现了一种新型的嵌合mRNA，该mRNA编码了一个假定的融合蛋白 1a蛋白的第一三分之一。根据我们的初步数据，提出了三个特定目标 旨在从根本上表征淋巴细胞中的5-羟色胺途径。第一个目的是 探索5-羟色胺是否是肿瘤淋巴细胞中的自分泌生存因子并扩展我们 了解5-羟色胺在原代幼稚辅助T细胞激活和分化中的作用的知识。这 该提案的第二个目的旨在在功能上表征新的1a融合笔录 淋巴细胞。该提案的最后目的旨在解决 通过其同源受体转导的血清素能信号。为此，我们将剖析 与T细胞系中的5-HT 1B受体相关的相关信号转导途径和一级T中的相关信号转导途径 细胞。 基本上，该建议旨在探索5-羟色胺的作用（神经递质，以其著名 参与控制情绪反应的控制）在安装免疫反应中。我们假设这一点 5-羟色胺是免疫系统的关键调节剂。了解血清素能的性质和作用 免疫系统中的受体可能会导致新的治疗策略来对抗自动免疫 疾病并治疗与移植排斥相关的问题。