NTS Purinoreceptor in Integrative Cardiovascular Control

描述(申请人摘要)：孤束核是一种 延髓背侧处理内脏感觉的主要整合部位 与心血管控制和反射协调有关的信息 区域上不同的自主反应模式。NTS包含了丰富的 介导和调节NTS的神经递质/神经调节剂词汇 其中腺苷和三磷酸腺苷都与整合密切相关 自主神经活动的控制，从而控制心血管 功能。NTS内的腺苷水平随生理和 病理生理状态(如缺血、低血压出血、高 重力应力)。最近的研究有力地支持了这样一个概念 腺苷通过腺苷P1嘌呤受体发挥神经调节作用 在NTS的自主控制机制中。此外，还有几行 来自我们实验室和其他人的证据表明，ATP，作用 在P2x嘌呤受体上，作为NTS介导的快速递质物质 压力感受性反射控制外周循环的机制。几乎所有人 以前关于腺苷和三磷酸腺苷作用的研究仅限于 要么是在细胞水平上的影响，要么是只观察全球 心血管反应(例如，动脉压和心率的变化)。 由于心血管控制是一个高度一体化的过程， 显示出显著的区域差异，在生理和 病理生理环境，我们的实验室结合了强大的 微量物质注入体内的方法 伴有复杂的外周心血管疾病的离散脑干区 能够监测区域血管和传出神经的仪器 开发一种独特的动物模型以研究其发病机制的活动 NTS利用“最新技术”调节心血管控制 方法论和分析技术。这项提案中描述的研究包括 重点确定功能重要性和传出机制 腺苷和三磷酸腺苷在NTS内起作用，调节和修饰整合 心血管系统的控制。这些研究将显著增加 我们对在会议上确定的过程的功能重要性的理解 心血管控制综合协调中的细胞水平 机制，并可能有助于开发新的药理学方法来治疗 心血管功能中枢神经支配改变的治疗。

DESCRIPTION (Applicant's abstract): The nucleus tractus solitarius (NTS) is a major integrative site in the dorsal medulla for processing viscerosensory information involved in cardiovascular control and reflex coordination of regionally distinct autonomic response patterns. The NTS contains a rich vocabulary of neurotransmitters/neuromodulators mediating and modulating NTS integration among which both adenosine and ATP have been strongly implicated in the control of autonomic nerve activity and hence control of cardiovascular function. Adenosine levels within the NTS vary with both physiological and pathophysiological states (e.g., ischemia, hypotensive hemorrhage, high gravitational stress). Recent studies strongly support the concept that adenosine, acting via adenosine P1 purinoceptors, plays a neuromodulatory role in the mechanisms of autonomic control by the NTS. In addition, several lines of evidence from our laboratory and by others have suggested that ATP, acting at P2x purinoceptors, serves as a fast transmitter substance in NTS-mediated mechanisms of baroreflex control of the peripheral circulation. Nearly all previous studies regarding the actions of adenosine and ATP were restricted to either the effects at the cellular level or to observing only global cardiovascular responses (e.g., changes in arterial pressure and heart rate). Inasmuch as cardiovascular control is a highly integrative process and demonstrates marked regional variability in both physiological and pathophysiological settings, our laboratory has combined the powerful approaches of microinjection of very small quantities of substances into discrete brainstem areas with sophisticated peripheral cardiovascular instrumentation capable of monitoring regional vascular and efferent neural activities to develop a unique animal model to investigate the mechanisms of modulation of cardiovascular control by the NTS utilizing "state-of-the-art" methodologies and analytical techniques. Studies described in this proposal are focused on determining the functional importance and efferent mechanisms whereby adenosine and ATP act within the NTS to mediate and modify integrative control of the cardiovascular system. These studies will significantly increase our understanding of the functional importance of processes identified at the cellular level in the integrative coordination of cardiovascular control mechanisms and may aid in the development of new pharmacological approaches to the treatment of altered central neural control of cardiovascular function.