SIGNAL TRANSDUCTION IN VASCULAR SMOOTH MUSCLE
血管平滑肌的信号转导
基本信息
- 批准号:6110456
- 负责人:
- 金额:$ 25.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-01-01 至 2000-12-31
- 项目状态:已结题
- 来源:
- 关键词:CHO cells G protein adenosine adenylate cyclase biological signal transduction cell cycle congestive heart failure guanylate cyclase membrane proteins neurotransmitter receptor phospholipase C phosphorylation receptor coupling recombinant DNA tissue /cell culture transfection vascular smooth muscle western blottings
项目摘要
Adenosine receptors (AR) play a major role in maintaining and regulating
cardiovascular function. The physiological effects of adenosine range from
control of chronotropy and ionotropy to vasoregulation and the modulation
of growth and migration of smooth muscle cells. Congestive heart failure
is associated with decreased vasoregulatory response to adenosine and small
vessel vasospasm. In this project, the investigators will characterize AR
mediated transmembrane signalling in vascular smooth muscle cells (VSMC)
including a delineation of which AR are present, which effector systems are
utilized in signalling, how AR regulate growth and differentiation, how
elevated levels of adenosine regulate these receptor systems and how these
functions can be modified through creation of mutant ARs with particular
emphasis on AZARs. Evidence will also be sought to determine if the newly
found A2b and A3AR are present in VSMC since physiological data are
consistent with their presence. Studies will be carried out in primary
cultures of VSMCs, a transformed VSMC line and in CHO and COS7 cells
transfected with wild type or mutant receptors. The process of
desensitization will be probed in detail concerning the role of
phosphorylation of the receptor, mechanisms by which the cell cycles AR and
how mutation of potential regulatory sites on the AR changes the patterns
of desensitization. Strong evidence exists that the A1AR can regulate
multiple effector systems in VSMCs including adenylylcyclase, phospholipase
C and guanylate cyclase. A2AR receptors appear to only stimulate
adenylylcyclase. Evidence suggests that activation of A2ARs inhibit and
A1ARs stimulate growth and DNA synthesis in VSMC. These pathways will be
studied in detail and approaches to selectively differentiate pathways that
lead to regulation of muscle tone such as inhibition of adenylylcyclase
versus regulation of growth and DNA synthesis which may well be mediated by
phospholipase C will be undertaken. Attempts to modulate growth of SMCs
through transfection (infection) of mutant receptors such as constitutively
active AR or dominant negative AR will be undertaken using high efficiency
adenovirus vectors. The overall goal will be to understand AR mediated
transmembrane signalling in VSMCs, how it is regulated and how it is
possible to manipulate these pathways via recombinant DNA techniques for
potential therapeutic benefit.
腺苷受体(Adenosine receptor, AR)在维持和调节细胞生长中起着重要作用
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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GARY L STILES其他文献
GARY L STILES的其他文献
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{{ truncateString('GARY L STILES', 18)}}的其他基金
PHARMACOLOGY OF CARDIAC A1 ADENOSINE RECEPTORS
心脏 A1 腺苷受体的药理学
- 批准号:
3348744 - 财政年份:1986
- 资助金额:
$ 25.99万 - 项目类别:
PHARMACOLOGY OF CARDIAC A1 ADENOSINE RECEPTORS
心脏 A1 腺苷受体的药理学
- 批准号:
3348738 - 财政年份:1986
- 资助金额:
$ 25.99万 - 项目类别:
PHARMACOLOGY OF CARDIAC A1 ADENOSINE RECEPTORS
心脏 A1 腺苷受体的药理学
- 批准号:
2217746 - 财政年份:1986
- 资助金额:
$ 25.99万 - 项目类别:
PHARMACOLOGY OF CARDIAC A1 ADENOSINE RECEPTORS
心脏 A1 腺苷受体的药理学
- 批准号:
3348745 - 财政年份:1986
- 资助金额:
$ 25.99万 - 项目类别:
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