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Arterial 5-HT Transporter Function

动脉5-HT转运蛋白功能

基本信息

批准号：
7585316
负责人：
Stephanie W Watts
金额：
$ 32.54万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7585316
关键词：
Abbreviations Acetates Acetic Acids Address Affinity Agonist Animals Anxiety Disorders Arteries Bathing Biochemistry Biological Assay Blood Pressure Blood Vessels Cardiovascular system Cell Culture Techniques Central Nervous System Agents Chemosensitization Contracts DOCA Deoxycorticosterone Disease Endothelin Endothelin-1 Fenclonine Hand Hormones Human Hydroxyindoleacetic Acid Hypertension Immunohistochemistry In Vitro Inbred SHR Rats Knowledge Laboratories Metabolism Methaqualone Mitogens Modeling Modification Monoamine Oxidase A Mus Muscle Muscle function Names Neurotransmitters Norepinephrine Obesity Peripheral Peripheral Resistance Phenylephrine Physiological Physiology 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 depression dopamine transporter experience feeding gastrointestinal hydroxyindole in vivo inhibitor/antagonist insight noradrenaline transporter programs receptor respiratory response serotonin receptor serotonin transporter tonin uptake

项目摘要

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