NEUTRAL ENDOPEPTIDASE AND CAROTID BODY FUNCTIONS
中性内肽酶和颈动脉体功能
基本信息
- 批准号:2222945
- 负责人:
- 金额:$ 17.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1995
- 资助国家:美国
- 起止时间:1995-06-07 至 1998-03-31
- 项目状态:已结题
- 来源:
- 关键词:acetylcholinesterase carotid body cats chemical structure function endopeptidases enkephalins enzyme activity hemorrhagic shock high performance liquid chromatography hypercapnia hyperoxia hypoxia immunoelectron microscopy laboratory rat microspectrophotometry molecular weight radioimmunoassay superior cervical ganglion sympathectomy western blottings
项目摘要
The carotid bodies are peripheral chemoreceptor organs. They transduce
changes in the levels of arterial oxygen, carbon dioxide, and hydrogen ion
concentrations into action potential encoded nerve signals. This
transduction process is believed to occur through a complex mechanism,
mediated by a variety of neurochemicals such as biogenic amines,
neuropeptides and gas molecules like nitric oxide. Our studies on the
metabolism of neuropeptides in the carotid body have shown that neutral
endopeptidase (NEP) plays a major role in the regulation of neuropeptides
like tachykinins and enkephalins in the carotid body. Also, we have found
that NEP in the carotid body occurs in two active forms viz., a less
common cytosolic and conventional membrane-bound form in near equal
proportions. Furthermore, inhibition of the NEP activity in vivo appears
to potentiate the response of the carotid body to hypoxia suggesting that
the two NEP forms may play hitherto undefined important functional roles
in the carotid body. This investigation, specifically, addresses the
molecular characterization of the two NEP forms of the carotid body and
their importance in the function(s) of the carotid body.
Our hypothesis is that physiological stimulus such as hypoxia alters the
activity and/or synthesis of NEP. These changes in NEP, in turn, regulate
the concentrations and modulate the actions of both the excitatory and
inhibitory neuropeptides and thus determine the magnitude of chemosensory
responses of the carotid body to either acute and/or chronic hypoxia.
This hypothesis will be tested using biochemical and cellular biological
techniques in combination with immunological and immunocytochemical
studies on the two forms of NEP of the carotid body. Most of the
experiments will use carotid bodies obtained from cats and rats exposed to
defined gas challenges. Experiments outlined in Specific Aim 1 will
address the physico-chemical characterization of the soluble and membrane-
bound forms of NEP of the carotid body and evaluate the structural
relationship among the two NEP forms. The kinetic experiments proposed in
Specific Aim 2 will examine the possibility that the NEP forms of the
carotid body have different enzymological properties. In Specific Aim 3,
using immunocytochemical approaches, we will determine the cellular
location of NEP in relation to the location of tachykinins, enkephalins
and atrial natriuretic peptides in the carotid body. The potential
alterations in NEP forms of the carotid body in response to different gas
challenges and possible mechanisms involved in these alterations will be
addressed in Specific Aim 4. It is anticipated that the proposed studies
will provide clues as to the role of NEP in the functions of the carotid
body. These studies may also yield information in the development of
enzyme and its inhibitor(s) based therapeutic agents in the treatment of
hypoxemia, a major problem associated with chronic obstructive lung
diseases and high altitude adaptation.
颈动脉小体是外周化学感受器。他们转换
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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Ganesh K Kumar其他文献
Ganesh K Kumar的其他文献
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{{ truncateString('Ganesh K Kumar', 18)}}的其他基金
Neurotransmitter Metabolism in Intermittent Hypoxia
间歇性缺氧中的神经递质代谢
- 批准号:
7464291 - 财政年份:2008
- 资助金额:
$ 17.43万 - 项目类别:
Neurotransmitter Metabolism in Intermittent Hypoxia
间歇性缺氧中的神经递质代谢
- 批准号:
8050610 - 财政年份:2008
- 资助金额:
$ 17.43万 - 项目类别:
Neurotransmitter Metabolism in Intermittent Hypoxia
间歇性缺氧中的神经递质代谢
- 批准号:
7806365 - 财政年份:2008
- 资助金额:
$ 17.43万 - 项目类别:
Neurotransmitter Metabolism in Intermittent Hypoxia
间歇性缺氧中的神经递质代谢
- 批准号:
7587950 - 财政年份:2008
- 资助金额:
$ 17.43万 - 项目类别:
Neurotransmitter metabolism in intermittent hypoxia
间歇性缺氧中的神经递质代谢
- 批准号:
6580880 - 财政年份:2002
- 资助金额:
$ 17.43万 - 项目类别:
NEUTRAL ENDOPEPTIDASE AND CAROTID BODY FUNCTIONS
中性内肽酶和颈动脉体功能
- 批准号:
2222946 - 财政年份:1995
- 资助金额:
$ 17.43万 - 项目类别:
NEUTRAL ENDOPEPTIDASE AND CAROTID BODY FUNCTIONS
中性内肽酶和颈动脉体功能
- 批准号:
2392674 - 财政年份:1995
- 资助金额:
$ 17.43万 - 项目类别:
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