GENETICS OF ATRIAL NATRIURETIC FACTOR AND HYPERTENSION
GENETICS OF ATRIAL NATRIURETIC FACTOR AND HYPERTENSION
批准号:
3349725
负责人:
ROBERT M GRAHAM
金额:
$38.23万
依托单位国家:
美国
项目类别:
财政年份:
1989
资助国家:
美国
项目状态:
已结题
起止时间:
1989-09-30 至 1991-09-29
关键词:
Bartter's syndrome affinity chromatography atrial natriuretic peptide blood chemistry blood flow measurement body water complementary DNA dogs electrolyte balance electron microscopy familial hypertension genetic manipulation genetic transcription genetic translation heart cell high performance liquid chromatography histochemistry /cytochemistry homeostasis human subject hypertension immunochemistry immunoprecipitation laboratory mouse laboratory rabbit laboratory rat linkage mapping molecular cloning molecular genetics monoclonal antibody nucleic acid probes peptide chemical synthesis peptide structure protein biosynthesis radioimmunoassay radiotracer renal hypertension saluretic synthetic peptide tissue /cell culture
中文摘要
心房利钠因子(ANF)是最近发现的一种肽,
心房肌细胞内的特异性颗粒,具有强效利尿钠,
血管舒张性质。 虽然在以下方面取得了相当大的进展:
阐明其一级结构并分离和表征其
心钠素作为一种体液因子,在维持
心血管稳态,特别是与容量和血液有关的
压力控制几乎是未知的。 这是主要目的,
这是为了明确这个角色。 该方法是多学科的,
利用分子生物学、免疫化学和
生理学 转录和翻译控制机制将是
研究利用cDNA探针和免疫沉淀程序,
在培养的心房心肌细胞中定量ANF的产生,
具体的刺激。 将开发免疫化学技术来测量
血浆中ANF的水平,并确定其结构的储存,分泌
循环的形式。 完整的动物研究,特别是有意识的
仪器狗,将允许我们将ANF合成的变化(即,
转录和翻译调控)和释放到特定的
生理操作,包括肾周炎的发展
高血压,以及确定神经,血管和体液因素
来调节这些过程。 同样,在人类中的研究将是
开始定义ANF在维持容量和压力方面的作用
体内平衡 这些研究也将成为确定
可能代表遗传异常的潜在疾病
ANF生产的控制。 特别是,限制方法
片段长度分析以确定ANF基因或其
将利用邻近地区来确定与特定
可能预测到这种异常的疾病状态,例如
巴特和戈登综合征。 这些技术也将得到推广
为了验证ANF表达的遗传异常可能是
与某些形式的高血压的病因学有关。
英文摘要
Atrial natriuretic factor (ANF) is a recently discovered peptide stored in
specific granules within the atrial myocyte that has potent natriuretic and
vasorelaxant properties. Although considerable progress has been made in
elucidating its primary structure and in isolating and characterizing its
gene, the significance of ANF as a humoral factor in maintaining
cardiovascular homeostasis, particularly in relation to volume and blood
pressure control, is virtually unknown. It is the major aim of this
proposal to define this role. The approach is multidisciplinary and will
utilize methods from the fields of molecular biology, immunochemistry and
phsyiology. Transcriptional and translational control mechanisms will be
investigated utilizing CDNA probes and immunoprecipitation procedures to
quantitate ANF production in cultured atrial cardiocytes in response to
specific stimuli. Immunochemical techniques will be developed to measure
ANF levels in plasma and to determine the structure of the stored, secreted
and circulating forms. Intact animal studies, in particular the conscious
instrumented dog, will allow us to relate changes in ANF synthesis (i.e.
transcriptional and translational regulation) and release to specific
physiological manipulations, including the development of perinephritic
hypertension, as well as to define the neural, vascular and humoral factors
that regulate these processes. Similarly, stu7dies in humans will be
initiated to define the role of ANF in maintaining volume and pressure
homeostasis. These studies will also form the basis for identifying
potential diseases that ;may represent abnormalities in the genetic
regulation of ANF production. In particular, the method of restriction
fragment length analysis to define polymorphisms in the ANF gene or in its
vicinity will be utilized to identify potential linkage with particular
disease states where such an abnormality might be predicted, such as
Bartter's and Gordon's syndromes. These techniques will also be extended
to test the hypothesis that a genetic abnormality in ANF expression may be
involved in the etiology of certain forms of hypertension.
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Ouabain induces secretion of proatrial natriuretic factor by rat atrial cardiocytes.
哇巴因诱导大鼠心房心肌细胞分泌心房钠尿因子。
DOI:
10.1152/ajpendo.1988.255.3.e383
发表时间:
1988
期刊:
The American journal of physiology
影响因子:
--
作者:
[Bloch,KD, Zamir,N, Lichtstein,D, Seidman,CE, Seidman,JG]
通讯作者:
Seidman,JG
Analysis of atrial natriuretic factor biosynthesis and secretion in adult and neonatal rat atrial cardiocytes.
成年和新生大鼠心房心肌细胞心房钠尿因子生物合成和分泌的分析。
DOI:
10.1016/0024-3205(87)90748-x
发表时间:
1987
期刊:
Life sciences
影响因子:
6.1
作者:
[Zisfein,JB, Sylvestre,D, Homcy,CJ, Graham,RM]
通讯作者:
Graham,RM
Characterization and purification of a protease in serum that cleaves proatrial natriuretic factor (ProANF) to its circulating forms.
血清中一种蛋白酶的表征和纯化,该蛋白酶可将心房钠尿因子 (ProANF) 裂解为其循环形式。
DOI:
10.1021/bi00400a030
发表时间:
1987
期刊:
Biochemistry
影响因子:
2.9
作者:
[Zisfein,JB, Graham,RM, Dreskin,SV, Wildey,GM, Fischman,AJ, Homcy,CJ]
通讯作者:
Homcy,CJ
cis-dominance of rat atrial natriuretic factor gene regulatory sequences in transgenic mice.
转基因小鼠中大鼠心房钠尿因子基因调控序列的顺式显性。
DOI:
10.1139/y91-223
发表时间:
1991
期刊:
Canadian journal of physiology and pharmacology
影响因子:
2.1
作者:
[Seidman,CE, Schmidt,EV, Seidman,JG]
通讯作者:
Seidman,JG
Serum-mediated enhancement of ANF accumulation in the culture medium of cardiac atriocytes.
血清介导的心肌细胞培养基中 ANF 积累的增强。
DOI:
10.1016/0006-291x(86)91070-3
发表时间:
1986
期刊:
Biochemical and biophysical research communications
影响因子:
3.1
作者:
[Sylvestre,DL, Zisfein,JB, Graham,RM, Homcy,CJ]
通讯作者:
Homcy,CJ
共 7 条
SCOR IN HYPERTENSION
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批准号:3106707
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项目类别:
-
资助金额:$69.06万
-
财政年份:1990
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-
依托单位:
SCOR IN HYPERTENSION
-
批准号:3106708
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-
资助金额:$68.17万
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财政年份:1990
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负责人:ROBERT M GRAHAM
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依托单位:
ALPHA-RECPTOR PURIFICATION & ROLE IN NEUROTRANSMISSION
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资助金额:$16.57万
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ALPHA-RECPTOR PURIFICATION & ROLE IN NEUROTRANSMISSION
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资助金额:$17.98万
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负责人:ROBERT M GRAHAM
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依托单位:
ALPHA-RECEPTOR PURIFICATION ROLE IN NEUROTRANSMISSION
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批准号:3399690
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项目类别:
-
资助金额:$18.76万
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财政年份:1989
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负责人:ROBERT M GRAHAM
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依托单位:
ALPHA-RECEPTOR PURIFICATION ROLE IN NEUROTRANSMISSION
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批准号:3399692
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项目类别:
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资助金额:$22.45万
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财政年份:1989
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负责人:ROBERT M GRAHAM
-
依托单位:
GENETICS OF ATRIAL NATRIURETIC FACTOR AND HYPERTENSION
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批准号:3349724
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项目类别:
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资助金额:$34.19万
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财政年份:1985
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负责人:ROBERT M GRAHAM
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依托单位:
GENETICS OF ATRIAL NATRIURETIC FACTOR AND HYPERTENSION
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批准号:3349722
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项目类别:
-
资助金额:$41.38万
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财政年份:1985
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负责人:ROBERT M GRAHAM
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依托单位:
SCOR IN HYPERTENSION
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批准号:3106702
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项目类别:
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资助金额:$66.96万
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财政年份:1985
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负责人:ROBERT M GRAHAM
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依托单位:
GENETICS OF ATRIAL NATRIURETIC FACTOR AND HYPERTENSION
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批准号:3349723
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项目类别:
-
资助金额:$40.18万
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财政年份:1985
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负责人:ROBERT M GRAHAM
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依托单位:
GENETICS OF ATRIAL NATRIURETIC FACTOR AND HYPERTENSION
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批准号:3349721
-
项目类别:
-
资助金额:$42.25万
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财政年份:1985
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负责人:ROBERT M GRAHAM
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依托单位:
ALPHA-RECEPTOR PURIFICATION & ROLE IN NEUROTRANSMISSION
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项目类别:
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资助金额:$18.85万
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财政年份:1982
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负责人:ROBERT M GRAHAM
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依托单位:
ALPHA-RECEPTOR PURIFICATION ROLE IN NEUROTRANSMISSION
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批准号:3399689
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项目类别:
-
资助金额:$14.2万
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财政年份:1982
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负责人:ROBERT M GRAHAM
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依托单位:
ALPHA-RECEPTOR PURIFICATION ROLE IN NEUROTRANSMISSION
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批准号:3399688
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项目类别:
-
资助金额:$12.88万
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财政年份:1982
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负责人:ROBERT M GRAHAM
-
依托单位:
ALPHA-RECEPTOR PURIFICATION ROLE IN NEUROTRANSMISSION
-
批准号:3399687
-
项目类别:
-
资助金额:$12.78万
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财政年份:1982
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负责人:ROBERT M GRAHAM
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依托单位:
海外基金