PLATELET A2-ADRENORECEPTOR REGULATION IN HYPERTENSION
PLATELET A2-ADRENORECEPTOR REGULATION IN HYPERTENSION
批准号:
3342523
负责人:
ALAN S HOLLISTER
金额:
$10.83万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1984
资助国家:
美国
项目状态:
已结题
起止时间:
1984-07-01 至 1987-06-30
中文摘要
我们最近描述了激动剂诱导的α 2-肾上腺素受体
完整正常人血小板的脱敏和亲和力降低
出现在生理浓度的儿茶酚胺中。 这些研究
表明循环中儿茶酚胺持续调节血小板
α 2-肾上腺素受体激动剂的亲和力和敏感性。 相比之下,我们
初步研究表明,原发性高血压患者很少或没有
血小板α 2-肾上腺素受体激动剂亲和力的变化
生理刺激和激动剂诱导的脱敏延迟,
体外 该补助金的目的是进一步定义Alpha中的缺陷
2-高血压中的肾上腺素受体调节。 此外,由于
高血压与钠的异常细胞分布有关
和α 2-肾上腺素受体激动剂的亲和力受到以下因素的深刻影响
钠浓度,我们计划测试是否受体缺陷
调节与异常钠稳态有关。
高血压和血压正常的受试者将在治疗前和治疗后抽血。
在生理刺激改变血小板α 2-肾上腺素受体后,
激动剂亲和力正常。 聚合反应性,α
2-肾上腺素受体结合特性,血浆儿茶酚胺将
测定 钠离子浓度对受体结合的影响
完整和破碎的细胞制备物和激动剂诱导的脱敏
将在体外测定。 此外,控制钠摄入量
将评估钠对血小板α 2-肾上腺素受体的体内影响
敏感性和亲和力调节,对血小板内钠和钙
浓度,以及可能相互作用的血浆因子的存在
通过这些措施。
这些调查将阐明阿尔法的缺陷是否
2-高血压中的肾上腺素受体调节是由于异常鸟嘌呤
核苷酸调节蛋白功能,改变的钠稳态,和/或
血浆因子。 体外钠浓度研究将
区分钠“位点”,膜介导的钠
浓度效应或血浆因子作为血小板聚集的机制
血压正常者和高血压者的α 2肾上腺素受体调节。
这些研究将进一步深入了解
改变受体亲和力和调节高血压。
英文摘要
We have recently described agonist induced Alpha 2-adrenoreceptor
desensitization and affinity reduction in intact normal human platelets
occurring at physiological concentrations of catecholamines. These studies
indicate that circulating catecholamines continuously modulate platelet
Alpha 2-adrenoreceptor agonist affinity and sensitivity. In contrast, our
preliminary studies indicate that essential hypertensives show little or no
change in platelet Alpha 2-adrenoreceptor agonist affinity after
physiological stimuli and a delay in agonist-induced desensitization in
vitro. The purpose of this grant is to define further the defect in Alpha
2-adrenoreceptor regulation in hypertension. In addition, since essential
hypertension is associated with abnormal cellular distribution of sodium
and Alpha 2-adrenoreceptor agonist affinity is profoundly affected by
sodium concentration, we plan to test whether the defect in receptor
regulation is associated with abnormal sodium homeostasis.
Hypertensive and normotensive subjects will have blood drawn before and
after physiological stimuli which alter platelet Alpha 2-adrenoreceptor
agonist affinity in normals. Aggregatory responsiveness, Alpha
2-adrenoreceptor binding characteristics, and plasma catecholamines will be
determined. The effect of sodium concentration on receptor binding with
intact and broken cell preparations and on agonist-induced desensitization
will be determined in vitro. In addition, manipulation of sodium intake
will assess in vivo effects of sodium on platelet Alpha 2-adrenoreceptor
sensitivity and affinity regulation, on intraplatelet sodium and calcium
concentration, and on the presence of a plasma factor which may interact
with these measures.
These investigations will elucidate whether the defect in Alpha
2-adrenoreceptor regulation in hypertension is due to abnormal guanine
nucleotide regulatory protein function, altered sodium homeostasis, and/or
a plasma factor(s). The in vitro sodium concentration studies will
distinguish between a sodium "site," a membrane-mediated sodium
concentration effect, or a plasma factor(s) as a mechanism for platelet
Alpha 2-adrenoreceptor regulation in normotensives and hypertensives.
These studies will yield further insight into the molecular mechanisms of
altered receptor affinity and regulation in hypertension.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
The potent pressor effect of phenylpropanolamine in patients with autonomic impairment.
苯丙醇胺对自主神经功能障碍患者的有效升压作用。
DOI:
--
发表时间:
1987
期刊:
JAMA
影响因子:
--
作者:
[Biaggioni,I, Onrot,J, Stewart,CK, Robertson,D]
通讯作者:
Robertson,D
CARDIOVASCULAR PHARMACOLOGY OF ATRIAL NATRIURETIC FACTOR
-
批准号:3352436
-
项目类别:
-
资助金额:$15.68万
-
财政年份:1987
-
负责人:ALAN S HOLLISTER
-
依托单位:
CARDIOVASCULAR PHARMACOLOGY OF ATRIAL NATRIURETIC FACTOR
-
批准号:3352437
-
项目类别:
-
资助金额:$6.13万
-
财政年份:1987
-
负责人:ALAN S HOLLISTER
-
依托单位:
CARDIOVASCULAR PHARMACOLOGY OF ATRIAL NATRIURETIC FACTOR
-
批准号:3352438
-
项目类别:
-
资助金额:$9.62万
-
财政年份:1987
-
负责人:ALAN S HOLLISTER
-
依托单位:
CARDIOVASCULAR PHARMACOLOGY OF ATRIAL NATRIURETIC FACTOR
-
批准号:3352432
-
项目类别:
-
资助金额:$17.2万
-
财政年份:1987
-
负责人:ALAN S HOLLISTER
-
依托单位:
CARDIOVASCULAR PHARMACOLOGY OF ATRIAL NATRIURETIC FACTOR
-
批准号:3352435
-
项目类别:
-
资助金额:$16.58万
-
财政年份:1987
-
负责人:ALAN S HOLLISTER
-
依托单位:
PLATELET A2-ADRENORECEPTOR REGULATION IN HYPERTENSION
-
批准号:3342522
-
项目类别:
-
资助金额:$10.47万
-
财政年份:1984
-
负责人:ALAN S HOLLISTER
-
依托单位:
PHARMACOKINETICS OF CONTROLLED RELEASE AND REGULAR FORMULATIONS OF AZT
-
批准号:3762491
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
INTERRELATION OF ANF SECRETAGOGUES AND PLASMA ANF IN HYPERTENSION
-
批准号:3740122
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
CORE--LABORATORY CORE
-
批准号:3779729
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
PLATELET ALPHA 2-ADRENORECEPTOR REGULATION IN HYPERTENSION
-
批准号:3899420
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
CORE--LABORATORY CORE
-
批准号:3757805
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
INFUSION OF ATRIAL NATRIURETIC FACTOR AND SYMPATHETIC NERVOUS SYSTEM
-
批准号:3863911
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
USE OF MIDODRINE IN ORTHOSTATIC HYPOTENSION
-
批准号:3740164
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
LABORATORY CORE
-
批准号:3858296
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
COMPARATIVE SURROGATE MARKER EFFICACY OF AZTEC VS RETROVIR
-
批准号:3762508
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
PHARMACOKINETICS OF CONTROLLED RELEASE AND REGULAR FORMULATIONS OF AZT
-
批准号:3740166
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
PLATELET ALPHA 2-ADRENORECEPTOR REGULATION IN HYPERTENSION
-
批准号:3879219
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
ALCOHOLISM IN NATIVE AMERICANS
-
批准号:3740107
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
USE OF MIDODRINE IN ORTHOSTATIC HYPOTENSION
-
批准号:3762489
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
PLATELET ALPHA 2-ADRENORECEPTOR REGULATION IN HYPERTENSION
-
批准号:3920379
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ALAN S HOLLISTER
-
依托单位:
海外基金