Signal Transduction in Intrapulmonary Chemoreceptors

肺内化学感受器的信号转导

基本信息

批准号：
7981434
负责人：
STEVEN C HEMPLEMAN
金额：
$ 43.97万
依托单位：
NORTHERN ARIZONA 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：
2007-02-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7981434
关键词：
4-Aminopyridine ATP phosphohydrolase Aerobic Affect Amiloride Ammonium Chloride Anesthetics Anoxia Apamin Arizona Automobile Driving Bicarbonates Biomedical Research Birds Blood flow Breathing Buffers Calcium Carbon Dioxide Cell membrane Characteristics Charybdotoxin Chemoreceptors Complication Coupled Coupling Dehydration Dependence Disease Economic Inflation Energy Metabolism Environmental air flow Esomeprazole Frequencies Future Gases Glyburide H(+)-K(+)-Exchanging ATPase Hand Hand functions Health Human Hydration status Infusion procedures Intracellular Transport Intravenous Ion Channel Laboratories Lactic acid Left lung Left pulmonary artery Lung Mammals Mechanoreceptors Medical Membrane Metabolic Modeling Na(+)-K(+)-Exchanging ATPase Neurons Ouabain Oxalates Oxygen Pathway interactions Patients Pharmaceutical Preparations Phylogenetic Analysis Play Potassium Potassium Channel Process Production Property Proton-Translocating ATPases Protons Pulmonary Heart Disease Pulmonary Stretch Receptors Regulation Research Role Scientist Signal Transduction Stimulus Stomach Stream Stretching Sulfonylurea Compounds Testing Tolbutamide Training Universities Vertebrates Work anaerobic glycolysis antiport carbonate dehydratase career cost effective therapy experience gadolinium chloride graduate student inhibitor/antagonist interest ion channel blocker mind control public health relevance pyridine relating to nervous system research study respiratory response sensor

项目摘要

DESCRIPTION (provided by applicant): We will study the cellular mechanisms of CO2 transduction in avian intrapulmonary chemoreceptors (IPC) as a model for general principles of respiratory CO2 transduction in vertebrates. We will use this research to introduce undergraduate and graduate students at Northern Arizona University to biomedical research using hands-on lab experiences and training in scientific practice. Aim I of this proposal will test whether active proton transport by v-type H+ ATPase and H+/K+-ATPase participate in pH regulation and CO2 transduction in IPC. Concanomycin A and esomeprazole will be used while recording single unit chemoreceptor responses to phasic CO2 stimuli. Aim II will test whether transient lactic acid accumulation or KATP channels play roles in IPC spike frequency adaptation (SFA), using lactate infusion and glibenclamide with single-unit recordings. Aim III will test the hypothesis that IPC share some signal transduction properties found in mammalian CO2-sensitive pulmonary stretch receptors (PSR), which would indicate a degree of phylogenetic homology between PSR and IPC. 4-amino pyridine, a fast K+ ion channel blocker shown to decrease PSR response to CO2, and gadolinium chloride, a blocker of stretch activated ion channels which impairs PSR response to lung inflation, will be studied in single-unit IPC. Aim IV will investigate the role of Na+/K+ ATPase in energizing the IPC membrane and influencing Ca++ levels via Na+/Ca++ exchange. This research will enhance understanding of respiratory chemoreceptors in general, attract and train of future scientists at NAU, and may suggest medical treatments useful for treating disorders in CO2 chemosensitivity. PUBLIC HEALTH RELEVANCE: This research investigates fundamental neural processes that detect CO2 levels in the body and send neural signals to the brain that control breathing. This is important for human health, because better understanding of respiratory CO2 chemotransduction may help develop more effective treatments and drugs for the loss of CO2 chemosensitivity, a common complication seen in patients with severe cardiopulmonary disease. The research will also be used to stimulate interest and give hands-on scientific experience to undergraduate and graduate students at Northern Arizona University interested in biomedical research careers.

描述（由申请人提供）：我们将研究禽体内化学感受器（IPC）中二氧化碳转导的细胞机制，作为脊椎动物中呼吸道CO2转导的一般原理的模型。我们将使用这项研究将北亚利桑那大学的本科生和研究生介绍，以使用动手实验室经验和科学实践培训进行生物医学研究。该提案的目的I将测试V型H+ATPase和H+/K+-ATPase的主动质子转运是否参与IPC中的pH调节和CO2转导。记录单位化学感受器对阶段CO2刺激的单位化学感受器的反应时，将使用丙霉素A和埃索美丙唑。 AIM II将使用乳酸输注和单单元记录来测试瞬时乳酸积累或KATP通道在IPC Spike频率适应（SFA）中起作用。 AIM III将检验以下假设：IPC具有在哺乳动物CO2敏感的肺部拉伸受体（PSR）中具有的一些信号转导特性，该特性表明PSR和IPC之间有一定程度的系统发育同源性。 4-氨基吡啶，一种快速的K+离子通道阻滞剂，显示可降低对CO2的PSR响应，而氯化氯化吡啶则将在单单单元IPC中研究损害PSR对肺膨胀的拉伸激活离子通道的阻滞剂。 AIM IV将研究Na+/K+ATPase在通过NA+/CA ++交换来影响CA ++水平的Na+/K+ATPase在能量中的作用。这项研究将增强对NAU的未来科学家的一般呼吸学化学感受器的了解，并可能建议对治疗二氧化碳化学敏感性疾病有用的医疗治疗。公共卫生相关性：这项研究调查了检测体内二氧化碳水平并将神经信号传递到控制呼吸的大脑的基本神经过程。这对人类健康很重要，因为对呼吸道二氧化碳趋化转导的更好理解可能有助于开发更有效的治疗方法和药物，以使二氧化碳化学敏感性丧失，这是严重心肺疾病患者的常见并发症。这项研究还将用于刺激兴趣，并为北亚利桑那大学的本科和研究生提供动手科学经验，对生物医学研究职业感兴趣。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effects of aerobic and anaerobic metabolic inhibitors on avian intrapulmonary chemoreceptors.

DOI：
10.1152/ajpregu.90608.2008
发表时间：
2009-05
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Jason Q. Pilarski;I. Solomon;D. Kilgore;S. Hempleman
通讯作者：
Jason Q. Pilarski;I. Solomon;D. Kilgore;S. Hempleman

Comparative embryology of the carotid body.

颈动脉体的比较胚胎学。