Arterial 5-HT Transporter Function

5-羟色胺（5-HT，血清素）浓度的改变或受体刺激具有 导致了抑郁症、进食障碍和肥胖症的治疗。5-HT也是一种血管 平滑肌细胞有丝分裂原和血管收缩剂，但大量的工作已经产生 在控制全身血液中，5-HT在体内改变动脉张力方面的结果不明确 压力重要的是，5-HT与外周动脉功能的相关性受到质疑 因为动脉处理和5-HT代谢的机制尚不清楚。我们的整体 一种假说是血清素转运蛋白（SERT）存在于外周动脉中， 动脉功能的生理后果。我们将使用一套完整的技术- 分离的组织浴和肌电描记术，免疫组织化学，Western，细胞培养， 转运蛋白活性测定和遥测-在大鼠和小鼠中，以解决两个具体目标： 具体目的#1：检验5-HT从动脉摄取和释放的假设 平滑肌SERT。我们假设5-HT被主动摄取、释放， 可能储存在外周动脉中，功能依赖于SERT。这些发现建立了一个 对于动脉中的局部肾上腺素能系统的情况，应该调节系统， 如果在生理上重要，则可以修改。因此，这方面的工作是为了了解 SERT的功能调节和测试是否存在会形成 局部5-HT系统：合成、摄取、储存和释放。 具体目标#2：检验SERT改变动脉功能的假设， 生理后果这个目标建立在目标1的基础上，通过研究两个模型，其中SERT 功能具有生理相关性，因此能够说明 5-HT/SERT，因为它涉及改变动脉收缩力和血压。第一模型 阈下浓度的5-HT增强动脉收缩的动脉， 去甲肾上腺素和内皮素，第二个高血压模型。 总的来说，这些研究很重要，因为它们突出了5-HT在 外周心血管系统，并揭示了SERT的新的功能作用。此外，委员会认为， 因为SERT是常用的5-羟色胺再摄取抑制剂的靶点， 百忧解，这些研究提供了潜在的洞察心血管并发症经历 那些服用SERT抑制剂的人。

Modification of 5-hydroxytryptamine (5-HT, serotonin) concentration or receptor stimulation has resulted in treatments for depression, feeding disorders and obesity. 5-HT is also a vascular smooth muscle cell mitogen and vasoconstrictor but a significant amount of work has produced equivocal results in terms of 5-HT modifying arterial tone in vivo in the control of systemic blood pressure. Importantly, the relevance of 5-HT to peripheral arterial function has been questioned because mechanisms for arterial handing and metabolism of 5-HT are unknown. Our overall hypothesis is that the serotonin transporter (SERT) is present in peripheral arteries and has physiological consequence in arterial function. We will use an integrated set of techniques - isolated tissue baths and myographs, immunohistochemistry, Westerns, cell culture, transporter activity assays, and telemetry -- in rats and mice to address two specific Aims: Specific Aim #1: To test the hypothesis that 5-HT is taken up and released from arterial smooth muscle by SERT. We hypothesize that 5-HT is actively taken up, released and potentially stored in peripheral arteries, functions dependent on SERT. Such findings build a case for a local serotonergic system in the artery, a system which should be regulated and modifiable if physiologically important. Thus, work in this aim is directed towards understanding functional regulation of SERT and testing for the presence of components that would form a local 5-HT system: synthesis, uptake, storage and release. Specific Aim #2: To test the hypothesis that SERT modifies arterial function with physiological consequence. This aim builds on Aim 1 by studying two models in which SERT function has physiological relevance and thus enables illustration of the importance of 5-HT/SERT as it relates to modifying arterial contractility and blood pressure. The first model is the artery in which subthreshpld concentrations of 5-HT potentiate arterial contraction to norepinephrine and endothelin, the second a model of hypertension. Collectively, these studies are important because they highlight the role of 5-HT in the peripheral cardiovascular system, and reveal a new functional role for SERT. Moreover, because SERT is a target for the commonly prescribed serotonin reuptake inhibitors such as Prozac¿, these studies provide potential insight into cardiovascular complications experienced by those taking SERT inhibitors.