UWY COBRE: NEUROPEPTIDE SIGNALING IN CONTROL OF SALT INTAKE & BLOOD PRESSURE

UWY COBRE：控制盐摄入量的神经肽信号传导

• 批准号: 7381215
• 负责人: FRANCIS W FLYNN
• 金额: $ 38.99万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381215
• 关键词: baroreceptors; baroreflex; blood pressure; bradycardia; brain; cardiovascular function; cell membrane; dendrites; hypertension; immunocytochemistry; neurons; neuropeptides; peptides; receptor; receptor binding; role; salt intake; solitary tract nucleus; substance P; suppression; tachykinin

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The present studies are directed at studying the brain mechanisms controlling salt intake and cardiovascular function. The brain tachykinins, substance P (SP) and neurokinin B (NKB), are implicated in the pathogenic mechanisms underlying hypertension. To further investigate the functions of SP and NKB in cardiovascular signaling, we visualized, using immunohistochemistry, the internalization of SP receptors (NK1) and NKB (NK3) receptors in the nucleus of the solitary tract following increases in blood pressure. In control animals, NK1 and NK3 receptor immunohistochemistry revealed that the recepotrs were distributed along the plasma membrane. Activation of baroreceptors was accompanied by the appearance of finely-beaded dendrites of NST neurons. This appearance is attributed to the release of SP and the internalization of the NK1 receptor. In addition, we show that activation of baroafferents results in the internalization of NK3 receptors in the NST. Exogenous injection of NK3 receptor agonists decreased the gain of the baroreflex, which was due to a suppression of parasympathetic mediated bradycardia. Collectively, these results show a functional role of two tachykinin peptides in the control of blood pressure.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。本研究旨在研究控制盐摄入量和心血管功能的大脑机制。脑tachyinins，物质P（SP）和Neurokinin B（NKB）与高血压的致病机制有关。为了进一步研究SP和NKB在心血管信号传导中的功能，我们使用免疫组织化学，SP受体（NK1）和NKB（NK3）受体的内在化在血压升高后的核中进行了内在化。在对照动物中，NK1和NK3受体免疫组织化学表明，将recepotrs分布在质膜上。压力感受器的激活伴随着阳性的NST神经元树突的出现。该外观归因于SP的释放和NK1受体的内在化。此外，我们表明，缓冲剂的激活导致NST中NK3受体的内在化。 NK3受体激动剂的外源注射减少了压力反射的增加，这是由于抑制了副交感神经介导的心动过缓。总的来说，这些结果表明了两种速肽肽在血压控制中的功能作用。