CHARACTERIZATION OF CENTRAL SEROTONIN RECEPTORS

焦点集中在耦合的两个中心型5HT2和5HT1c受体上 对肌醇脂代谢的影响，这些生理功能 受体及其调节机制。这些问题 将在所有层面上解决，从基因表达的分子研究 受体介导的生化和生理的细胞学研究 对整个动物行为和生理研究的反应 功能。具体问题是：(1)羽绒形成的机制是什么？ 5HT2受体密度的调节与术后反应性丧失 对抗性管理？这些研究将集中在非典型的 抗抑郁药-5-羟色胺拮抗剂米安色林。(2)。这是什么关系？ 5HT2行为敏感性与双重调控机制 5HT2受体识别位点和5HT2介导的猪的变化 水解法)。这些研究将比较两种生化指标 5HT2受体状态具有独特的行为模型，即 对功能相关的5HT2的变化具有双向敏感性 感受器。(3)失神经功能障碍的解释是什么 诱导，5HT2受体上调和反应性增强？一个 工作假说是神经元和神经胶质细胞上的5HT2受体受到调节 通过不同的机制掩盖神经元5HT2的适应性变化 受体。(4)5HT1c受体的生理作用是什么？这个 工作假说是5HT1c受体介导了5HT1c的营养效应。 5-羟色胺诱导脉络丛上皮细胞蛋白质合成增加 将以原代培养的细胞作为模型。(5)5HT1c怎么样？ 受体受调控吗？激动剂诱导亚敏感的机制及机制 将探讨拮抗剂诱导的下调，包括可能的 对5HT1c受体基因表达的影响。 所有这些工作的关键概念是当务之急是 细胞和组织中的生化研究与细胞中的功能有关 活着的动物。这一方法对于实现 最终目标是弥合以下实验室研究之间的差距 精神活性药物和精神疾病的临床治疗。

The focus in on two central 5HT receptor (5HT2 and 5HT1c) that are coupled to inositol lipid metabolism, the physiological functions of these receptors and the mechanisms by which they are regulated. These problems will be addressed at all levels, from molecular studies of gene expression to cellular studies of receptor-mediated biochemical and physiological responses to whole animal studies of behavioral and physiological functions. Specific questions are: (1) What is the mechanism of the down- regulation of 5HT2 receptor density and loss of responsiveness after antagonist administration? These studies will focus on the atypical antidepressant - 5HT antagonist, mianserin. (2). What is the relationship between 5HT2 behavioral sensitivity and the dual regulatory mechanisms (changes in 5HT2 receptor recognition site and in 5HT2-mediated PI hydrolysis). These studies will compare the two biochemical measures of the 5HT2 receptor state with a unique behavioral model that is bidirectionally sensitive to changes in functionally relevant 5HT2 receptors. (3) What is the explantation for the failure of denervation to elicit, 5HT2 receptor up-regulation and increased responsiveness? A working hypothesis is that 5HT2 receptors on neurons and glia are regulated by distinct mechanisms that mask adaptive changes in neuronal 5HT2 receptor. (4) What is the physiological role of 5HT1c receptors? The working hypothesis is that 5HT1c receptors mediate a trophic effect of 5HT. 5HT-induced elevation of protein synthesis in choroid plexus epithelial cells in primary culture will be used as a model. (5) How are 5HT1c receptors regulated? The mechanism of agonist-induced subsensitivity and of antagonist-induced down-regulation will be explored, including possible effects on the expression of the 5HT1c receptor gene. The key concept that underlies all of this work that it is imperative that biochemical studies in cells and tissues be related to function in the living animal. This approach is essential to the attainment of the ultimate goal of bridging the gap between laboratory studies of psychoactive drugs and clinical treatment of mental illness.