Effect/alveolar beta2 adrenergic receptor overexpression
Effect/alveolar beta2 adrenergic receptor overexpression
批准号:
6537926
负责人:
Phillip H Factor
金额:
$26.25万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-07-01 至 2003-05-31
关键词:
active transport beta adrenergic receptor beta antiadrenergic agent disease /disorder model gene therapy laboratory rat lung injury membrane permeability nonhuman therapy evaluation pulmonary edema receptor sensitivity respiratory airway clearance respiratory epithelium sodium channel sodium potassium exchanging ATPase transfection
中文摘要
描述(申请人提供):肺水肿已从
肺泡是钠从空域主动输送的结果,
肺泡上皮运输蛋白。已经观察到,在某些类型中
肺水肿时,这些主动清除机制受损。因此,
改善肺泡主动转运的方法可能被证明对
这种常见病的治疗。
据报道,β2-肾上腺素能激动剂可增加钠的活性,约
β2肾上腺素能受体转运和肺泡液体清除(ALC)
(β2 AR),长时间使用f3激动剂可降低β2 AR的表达
在肺泡上皮中。在本提案中包含的初步数据中,我们
已经观察到,药物剂量的β2-激动剂可使肺泡脱敏
Fβ2AR和肺泡β2AR的过度表达可增加ALC。这些
研究使我们假设:1)肺泡f32AR受制于
激动剂引起的功能丧失(脱敏),2)受体丧失
功能减弱儿茶酚胺反应的肺泡溶质转运,3)和
受体的过度表达可以通过改变
受体脱敏模式与功能细胞数目的增加
细胞膜上的受体。
为了检验这些假设,我们提出了三个相互关联的具体目标
将分子技术与生理学研究相结合以产生新的
对肺泡β2受体的作用和调节的见解:
具体目标#1:确定肺泡β2AR过度表达是否可以改善
受体功能和儿茶酚胺反应性ALC。具体目标2:测试
肺泡βAR可被约激动剂脱敏,如果脱敏
影响ALC,如果过度表达会减弱受体的脱敏作用。
具体目标#3:在实验模型中测试Beta2AR功能是否受损
肺损伤和IF受体功能的改善可以通过过度表达
急性肺损伤模型的建立。
心源性和非心源性肺水肿分别影响数百万人
这一年造成了相当大的发病率和死亡率。目前不存在
对这种危及生命的疾病的特殊治疗。这样做的目的是
建议提高我们对肺泡间相互作用的理解
β2受体和肺泡Na,K-ATPase,Na与通道和ALC有关。这个
此提案中包含的实验计划已被构建为允许我们
测试我们的假设并开发新的治疗方法来改善肺泡β2受体
功能和肺水肿清除。
英文摘要
DESCRIPTION (provided by applicant): Pulmonary edema is cleared from the
alveolus as a result of the active transport of Na+ out from the airspace by
alveolar epithelial transport proteins. It has been observed that in some types
of pulmonary edema these active clearance mechanisms are impaired. Thus,
methods that improve alveolar active transport may prove useful for the
treatment of this common condition.
It has been reported that beta2-adrenergic agonists increase active Na about
transport and alveolar liquid clearance (ALC) via beta2-Adrenergic Receptors
(beta2 AR) and that prolonged use of f3-agonists decreases beta2AR expression
in the alveolar epithelium. In preliminary data included in this proposal we
have observed that pharmacologic doses of a beta2-agonist desensitize alveolar
f beta2ARs and that alveolar beta2AR over expression increases ALC. These
studies caused us to hypothesize that: 1) alveolar f32ARs are subject to
agonist-induced loss of function (desensitization), 2) loss of receptor
function attenuates catecholamine responsive alveolar solute transport, 3) and
receptor over expression can positively affect these processes by altering
receptor desensitization patterns and increasing the number of functional
receptors in the cell membrane.
To test these hypotheses we are proposing three inter related specific aims
that integrate molecular techniques with physiologic studies to generate new
insights into the role and regulation of alveolar beta2ARs:
Specific Aim #1: To determine if alveolar beta2AR over expression can improve
receptor function and catecholamine responsive ALC. Specific Aim #2: To test if
alveolar beta AR's are desensitized by about agonists, if desensitization
affects ALC, and if over expression attenuates receptor desensitization.
Specific Aim #3: To test if beta2AR function is impaired in experimental models
of lung injury and if receptor function can be improved via over expression in
models of acute Lung injury.
Cardiogenic and non-cardiogenic pulmonary edema affect millions of people each
year causing substantial morbidity and mortality. Currently there exists no
specific treatment for this life-threatening condition. The goal of this
proposal is to improve our understanding of the interactions between alveolar
beta2ARs and alveolar Na, K-ATPases, Na about channels and ALC. The
experimental plan included in this proposal has been structured to allow us to
test our hypotheses and develop novel therapies to improve alveolar beta2AR
function and pulmonary edema clearance.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Effect of Traffic-Related Pollutants on Airway Beta2-Adrenergic Receptors
-
批准号:8279276
-
项目类别:
-
资助金额:$32.1万
-
财政年份:2011
-
负责人:Phillip H Factor
-
依托单位:
Adenosine Regulation of Alveolar Fluid Homeostasis
-
批准号:6856655
-
项目类别:
-
资助金额:$39.34万
-
财政年份:2005
-
负责人:Phillip H Factor
-
依托单位:
Adenosine Regulation of Alveolar Fluid Homeostasis
-
批准号:7162956
-
项目类别:
-
资助金额:$37.88万
-
财政年份:2005
-
负责人:Phillip H Factor
-
依托单位:
Adenosine Regulation of Alveolar Fluid Homeostasis
-
批准号:6998411
-
项目类别:
-
资助金额:$39.01万
-
财政年份:2005
-
负责人:Phillip H Factor
-
依托单位:
Adenosine Regulation of Alveolar Fluid Homeostasis
-
批准号:7333233
-
项目类别:
-
资助金额:$37.88万
-
财政年份:2005
-
负责人:Phillip H Factor
-
依托单位:
Role of airway epithelial Beta2-adrenergic receptors
-
批准号:6686968
-
项目类别:
-
资助金额:$36.79万
-
财政年份:2003
-
负责人:Phillip H Factor
-
依托单位:
Role of airway epithelial Beta2-adrenergic receptors
-
批准号:7109283
-
项目类别:
-
资助金额:$35.92万
-
财政年份:2003
-
负责人:Phillip H Factor
-
依托单位:
Role of airway epithelial Beta2-adrenergic receptors
-
批准号:6802703
-
项目类别:
-
资助金额:$36.79万
-
财政年份:2003
-
负责人:Phillip H Factor
-
依托单位:
Role of airway epithelial Beta2-adrenergic receptors
-
批准号:6941678
-
项目类别:
-
资助金额:$36.79万
-
财政年份:2003
-
负责人:Phillip H Factor
-
依托单位:
Effect/alveolar beta2 adrenergic receptor overexpression
-
批准号:6754524
-
项目类别:
-
资助金额:$28.49万
-
财政年份:2001
-
负责人:Phillip H Factor
-
依托单位:
Effect/alveolar beta2 adrenergic receptor overexpression
-
批准号:6383627
-
项目类别:
-
资助金额:$26.25万
-
财政年份:2001
-
负责人:Phillip H Factor
-
依托单位:
Alveolar epithelial B2-adrenergic receptors
-
批准号:7431602
-
项目类别:
-
资助金额:$34.12万
-
财政年份:2001
-
负责人:Phillip H Factor
-
依托单位:
Effect/alveolar beta2 adrenergic receptor overexpression
-
批准号:6638718
-
项目类别:
-
资助金额:$28.3万
-
财政年份:2001
-
负责人:Phillip H Factor
-
依托单位:
Alveolar epithelial B2-adrenergic receptors
-
批准号:7034569
-
项目类别:
-
资助金额:$35.14万
-
财政年份:2000
-
负责人:Phillip H Factor
-
依托单位:
Alveolar epithelial B2-adrenergic receptors
-
批准号:7228448
-
项目类别:
-
资助金额:$34.12万
-
财政年份:2000
-
负责人:Phillip H Factor
-
依托单位:
Alveolar epithelial B2-adrenergic receptors
-
批准号:6919592
-
项目类别:
-
资助金额:$35.31万
-
财政年份:2000
-
负责人:Phillip H Factor
-
依托单位:
Effect of Traffic-Related Pollutants on Airway Beta2-Adrenergic Receptors
-
批准号:7647419
-
项目类别:
-
资助金额:$29.73万
-
财政年份:--
-
负责人:Phillip H Factor
-
依托单位:
Effect of Traffic-Related Pollutants on Airway Beta2-Adrenergic Receptors
-
批准号:7325434
-
项目类别:
-
资助金额:$30.19万
-
财政年份:--
-
负责人:Phillip H Factor
-
依托单位:
Effect of Traffic-Related Pollutants on Airway Beta2-Adrenergic Receptors
-
批准号:7858269
-
项目类别:
-
资助金额:$31.86万
-
财政年份:--
-
负责人:Phillip H Factor
-
依托单位:
Effect of Traffic-Related Pollutants on Airway Beta2-Adrenergic Receptors
-
批准号:8080994
-
项目类别:
-
资助金额:$32.69万
-
财政年份:--
-
负责人:Phillip H Factor
-
依托单位:
海外基金