AGE AND VASCULAR ALPHA-ADRENOCEPTOR FUNCTIONAL COUPLING
年龄与血管α-肾上腺素受体功能耦合
基本信息
- 批准号:2002414
- 负责人:
- 金额:$ 7.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-02-27 至 1998-11-10
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Signal transduction for adrenergic receptors is regulated by a distinct
array of guanine nucleotide binding proteins (G proteins). Our
preliminary data indicate that in aorta, (alpha 1b-adrenoceptors (ARs)
are linked to both Go and Gq, while (alpha 1d)ARs couple exclusively to
Gq. In addition, the levels of various a1 AR subtypes in different
blood vessels were different. These results suggest that differential
coupling of a1 AR subtypes to G proteins may occur in different blood
vessels. These data furthermore suggest that age-related altering the
interaction of specific receptor and its associated G protein(s) may
significantly affect the receptor-mediated signaling and ultimately the
function of the organ. Changes in alpha-and B-AR functions in blood
vessels have been reported both in Fisher-344 rats and human. IN
addition, an age-related alterations in expression of (alpha)1AR
subtypes has also been observed in rat aorta. As aging plays an
significant role in mediating the pathogenesis of cardiovascular
disease, such as hypertension, orthostatic hypotension and
atherosclerosis, it is important to study the molecular mechanism (s)
contributing to altered vascular function during aging. The proposed
study aims to test the hypothesis that different compositions of alpha
(1)AR/G proteins regulate diverse arrays of transmembrane signalling
pathways n vasculature which are differentially affected by age. We are
proposing a series of experiments to fully characterize the contribution
of altered (alpha 1)ARv subtypes/G proteins coupling to the age-related
changes in (alpha 1) AR- mediated functions i vasculature.
Specifically, we will directly assess linkage of (alpha1) adrenoceptors
with G proteins in aortas and tail arteries from young and old rats.
Membranes prepared for blood vessels will be used to determine the
coupling of (alpha1)-adrenoceptor subtypes to G proteins by an
established immunoprecipitation procedure using specific anti-G(alpha)
or anti (alpha1 AR antibodies. In addition, we will define the
molecular mechanisms responsible for the changes in alpha1 AR
transduction systems during aging and test the specificity of these
alterations with respect to subclasses of (alpha1 AR, G proteins and
blood vessels. Results from the present proposal will greatly enhance
our knowledge of the role of the signal transduction pathways in the
pathophysiology of age-related cardiovascular diseases and ultimately
help in designing specific strategies for more effective pharmacotherapy
of those disorders in geriatric patients.
肾上腺素能受体的信号转导是由不同的
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Heterologous desensitization of the rat tail artery contraction and inositol phosphate accumulation after in vitro exposure to phenylephrine is mediated by decreased levels of Galphaq and Galphai.
体外暴露于去氧肾上腺素后,大鼠尾动脉收缩和磷酸肌醇积累的异源脱敏是由 Galphaq 和 Galphai 水平降低介导的。
- DOI:
- 发表时间:1997
- 期刊:
- 影响因子:0
- 作者:Seasholtz,TM;Gurdal,H;Wang,HY;Cai,G;Johnson,MD;Friedman,E
- 通讯作者:Friedman,E
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