NTS Adenosine Receptors in Cardiovascular Control

NTS 腺苷受体在心血管控制中的作用

基本信息

批准号：
7800969
负责人：
Donal S O'Leary
金额：
$ 37.63万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7800969
关键词：
Adenosine Adenosine A1 Receptor Adrenal Glands Adrenal Medulla Adrenergic Receptor Affect Agonist Antihypertensive Agents Baroreflex Blood Vessels Brain Stem Cardiopulmonary Cardiovascular system Cell Nucleus Cerebral Ischemia Chemoreceptors Complex Disinhibition Dorsal Dose Epinephrine Heart Heart Rate Hemorrhage Hindlimb Homeostasis Hypothalamic structure Kidney Laboratory Study Lateral Link Mediating Microinjections Middle Hypothalamus Nerve Neuraxis Neuromodulator Neurons Neurotransmitters Nucleus solitarius Output Pathway interactions Pattern Peripheral Physiological Play Pressoreceptors Process Purinergic P1 Receptors Purinoceptor Reflex action Reflex control Research Personnel Role Serotonin Site Skeletal Muscle Stress Structure Structure of area postrema Vasodilation Vasomotor Visceral Afferents Vocabulary autonomic nerve defense response gamma-Aminobutyric Acid neurotransmitter release paraventricular nucleus programs receptor relating to nervous system response restoration vascular bed

项目摘要

DESCRIPTION (provided by applicant): The nucleus tractus solitarius (NTS) is the major integrative center within the brainstem for cardiovascular homeostasis. The NTS receives primary input from a variety of cardiovascular afferents such as arterial and cardiopulmonary baroreceptors, peripheral chemoreceptors, somatic and visceral afferents. This information is integrated and via projections to the rostral and caudal ventro-lateral medulla (controlling efferent sympathetic activity) and to the ambiguous complex (controlling efferent parasympathetic activity), reflex control of autonomic nerve activity occurs. Integration of primary afferent information in the NTS can also be markedly affected by descending projections from higher central structures such as specific nuclei within the hypothalamus which have reciprocal connections with the NTS. The NTS neurons contain a rich vocabulary of neurotransmitters and neuromodulators which may affect NTS integration and therefore control of the cardiovascular system. Recently, we and others have shown that adenosine markedly affects NTS integration and thus can elicit profound changes in cardiovascular control. Adenosine levels in the NTS can rise via at least two distinct mechanisms, 1) during cerebral ischemia as occurs, for example, during marked hypotensive hemorrhage or high gravitational stress, and 2) via the breakdown of ATP released as a neurotransmitter or co-transmitter. Adenosine, acting pre-synaptically via both A1 or A2a receptors can modulate the extent of neurotransmitter release. Our previous studies strongly support the concept that different neurotransmitters/neuromodulators operating in the NTS are distinctly linked to specific patterns of regional cardiovascular and sympathetic responses archetypal for specific physiological and pathological situations. A key observation is the unique role of adenosine in the activation of pre-ganglionic adrenal sympathetic nerve activity which innervates the adrenal medulla. NTS adenosine receptor mediated activation of the adrenal medulla likely aids in the restoration of homeostasis during stress as well as likely contributes to the distinct cardiovascular patterns of the defense response. This competing renewal application is focused on 1) determining the mechanisms mediating the responses to stimulation of NTS adenosine receptor subtypes and 2) the role of adenosine receptors in the NTS in modulating cardiovascular responses from descending pathways and ascending peripheral inputs.

描述（由申请人提供）：核心索他叶核（NTS）是心血管稳态的脑干中的主要综合中心。 NTS从各种心血管传入，例如动脉和心肺压力感受器，外周化学感受器，体细胞和内脏传入等人中接收主要输入。这些信息是整合的，并通过投影到尾腹和腹侧腹侧髓质（控制传出的交感神经活动）和模棱两可的复合物（控制传出的副交感神经活动），自主神经活动的反射控制发生。 NTS中主要传入信息的整合也可能会受到来自较高中央结构（例如下丘脑内的特定核）的下降投影的明显影响，而下丘脑中与NTS具有相互连接。 NTS神经元包含丰富的神经递质和神经调节剂的词汇，这些词汇可能会影响NTS整合，从而控制心血管系统。最近，我们和其他人表明腺苷显着影响NTS整合，因此可以引起心血管控制的深刻变化。 NTS中的腺苷水平可以通过至少两种不同的机制上升，1）在大脑缺血期间，如在明显的低血压出血或高重力应力时发生的，而2）通过释放为神经递质或共晶剂的ATP崩溃。腺苷，通过A1或A2A受体在突触前作用，可以调节神经递质释放的程度。我们以前的研究强烈支持这样一个概念，即在NTS中运行的不同神经递质/神经调节剂与特定的心血管和交感神经反应的特定模式明显相关。一个关键的观察结果是腺苷在支配肾上腺髓质的伴形肾上腺交感神经活性的激活中的独特作用。 NTS腺苷受体介导的肾上腺髓质激活可能有助于在压力下恢复体内平衡，并且有可能有助于防御反应的独特心血管模式。这种竞争性更新应用的重点是1）确定介导对NTS腺苷受体亚型刺激的反应的机制，以及2）腺苷受体在NTS在调节心血管反应中的作用，从降落途径调节心血管响应和升高外围输入。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

严重出血会削弱心肺化学反射通过 NTS 腺苷受体对区域交感神经输出的控制。

DOI：
10.1152/ajpheart.00234.2014
发表时间：
2014
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
0
作者：
Minic,Zeljka;Li,Cailian;O'Leary,DonalS;Scislo,TadeuszJ
通讯作者：
Scislo,TadeuszJ

Sympathetic and parasympathetic component of bradycardia triggered by stimulation of NTS P2X receptors.

由 NTS P2X 受体刺激引发的心动过缓的交感神经和副交感神经成分。

DOI：
10.1152/ajpheart.00889.2005
发表时间：
2006
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
0
作者：
Kitchen,AmyM;O'Leary,DonalS;Scislo,TadeuszJ
通讯作者：
Scislo,TadeuszJ

Neural and humoral control of regional vascular beds via A1 adenosine receptors located in the nucleus tractus solitarii.

DOI：
10.1152/ajpregu.00565.2010
发表时间：
2011-03
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
J. Mcclure;D. O'Leary;T. Scislo
通讯作者：
J. Mcclure;D. O'Leary;T. Scislo

Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs.