Arterial 5-HT Transporter Function

动脉5-HT转运蛋白功能

• 批准号: 7382485
• 负责人: Stephanie W Watts
• 金额: $ 32.58万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382485
• 关键词: Abbreviations; Acetates; Acetic Acid; Acetic Acids; Address; Affinity; Agonist; Animals; Anxiety Disorders; Arteries; Bathing; Biochemistry; Biological Assay; Blood Pressure; Blood Vessels; Cardiovascular system; Central Nervous System Agents; Chemosensitization; Contracts; Cultured Cells; DOCA; Deoxycorticosterone; Disease; End Point; Endothelin; Endothelin-1; Fenclonine; Hand; High Blood Pressure; Hormones; Human; Hydroxyindoleacetic Acid; Hypertension; Immunohistochemistry; In Vitro; Inbred SHR Rats; Knowledge; Laboratories; Mental Depression; Metabolism; Methaqualone; Mitogens; Modeling; Modification; Monoamine Oxidase A; Mus; Muscle function; Names; Neurotransmitters; Norepinephrine; Obesity; Peripheral; Peripheral Resistance; Phenylephrine; Physiological; Physiology, Other; Process; Rat-1; Rattus; Regulation; Reproduction; Research; Research Personnel; Rodent; Role; Schizophrenia; Selective Serotonin Reuptake Inhibitor; Serotonin; Serum; Signal Pathway; Signal Transduction; Smooth Muscle; Smooth Muscle Myocytes; System; Techniques; Telemetry; Testing; Time; Tissues; Tryptophan 5-monooxygenase; Vasoconstrictor Agents; Work; dopamine transporter; experience; feeding; gastrointestinal; hydroxyindole; in vivo; inhibitor/antagonist; insight; noradrenaline transporter; programs; receptor; respiratory; response; serotonin receptor; serotonin transporter; tonin; uptake

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.

修饰5-羟色胺（5-HT， 5-羟色胺）浓度或刺激受体有