Brain Cannabinoid Receptor Signaling and Pharmacology
脑大麻素受体信号传导和药理学
基本信息
- 批准号:6706923
- 负责人:
- 金额:$ 31.98万
- 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:1997-01-10 至 2006-01-31
- 项目状态:已结题
- 来源:
- 关键词:CannabisG proteinbeta adrenergic receptorcalcium channelcannabinoid receptorcannabinoidsendogenous opioidenzyme activityganglionsgene targetinggenetically modified animalshippocampusimmunocytochemistrylaboratory ratneural inhibitionneuropharmacologynorepinephrinepotassium channelprotein kinase Aprotein structure functionreceptor couplingsomatostatin
项目摘要
DESCRIPTION (provided by applicant): Brain CB1 cannabinoid receptors are
involved in pain perception, appetite stimulation, learning and memory, the
tremor of multiple sclerosis and the rewarding effects of opiates. The basic
mechanisms of action of the CB1 cannabinoid receptor and their contributions to
these physiological and pathophysiological functions are unknown. We do know
that CB1 cannabinoid receptors inhibit neurotransmitter release and modulate
neuronal Ca2+ and K+ channels. Our lab found that CB1 cannabinoid receptors
tonically inhibit neuronal Ca2+ channels. We have new evidence that CB1
receptors not only modulate Ca2+ channels but that they also prevent other G
protein-coupled receptors from signaling. This novel type of inhibitory
cross-talk demonstrates that CB1cannabinoid receptors can function as dominant
receptors preventing other G protein-coupled receptors from signaling. Thus,
the cannabinoid receptor can influence neuronal activity not only when it is
tonically active or stimulated with an agonist but also by sequestering G
proteins and preventing other receptors from transducing their biological
signals. The degree of G protein sequestration appears to be related to the
density of CB1 receptors. Since the density of CB1 receptors is higher than any
other G protein-coupled receptor in the brain the ability of CB1 receptors to
prevent signaling by other G protein-coupled receptors is likely to be of
physiological significance in specific brain areas. Our overlying hypothesis is
that CB1 cannabinoid receptors not only modulate specific ion channels but also
sequester G proteins and prevent other G protein-coupled receptors from
signaling. It is not known if G protein sequestration is relevant to the
physiological functions of the CB1 cannabinoid receptor, and the mechanism of G
protein sequestration is completely unknown. We will determine whether
sequestration of G proteins by CB1 receptors is physiologically relevant and
the mechanism by which CB1 receptors sequester G proteins.
The specific aims of the proposed research will test the hypotheses that native
CB1 cannabinoid receptors prevent other receptors from signaling by
sequestering G proteins and that specific structural domains of the CB1
receptor contribute to tonic activity and the ability of CB1 cannabinoid
receptor to sequester G proteins.
描述(由申请人提供):脑CB 1大麻素受体是
参与疼痛感知,食欲刺激,学习和记忆,
多发性硬化症的震颤和阿片类药物的奖励作用。基本
CB 1大麻素受体的作用机制及其对
这些生理和病理生理功能是未知的。我们知道
CB 1大麻素受体抑制神经递质的释放,
神经元Ca ~(2+)和K ~+通道。我们的实验室发现CB 1大麻素受体
紧张性抑制神经元钙通道。我们有新的证据证明CB 1
受体不仅调节Ca 2+通道,而且还阻止其他G
蛋白偶联受体的信号传导。这种新型的抑制剂
cross-talk表明CB 1大麻素受体可以起主导作用,
受体阻止其他G蛋白偶联受体的信号。因此,在本发明中,
大麻素受体不仅可以影响神经元的活动,
具有紧张性活性或用激动剂刺激,但也可通过螯合G
蛋白质并阻止其他受体转导其生物活性
信号. G蛋白螯合的程度似乎与
CB 1受体密度。由于CB 1受体的密度高于任何
其他G蛋白偶联受体在大脑中的CB 1受体的能力,
阻止其他G蛋白偶联受体的信号传导可能是
在特定脑区的生理意义。我们的假设是
CB 1大麻素受体不仅调节特定的离子通道,
隔离G蛋白并阻止其他G蛋白偶联受体
信号尚不清楚G蛋白螯合是否与
CB 1大麻素受体的生理功能,以及G
蛋白质螯合是完全未知的。我们将决定
CB 1受体对G蛋白的螯合是生理相关的,
CB 1受体隔离G蛋白的机制。
拟议的研究的具体目标将测试的假设,
CB 1大麻素受体通过以下方式阻止其他受体的信号传导:
隔离G蛋白和CB 1的特定结构域
受体有助于紧张活性和CB 1大麻素的能力
受体来隔离G蛋白。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('DEBORAH L LEWIS', 18)}}的其他基金
Brain Cannabinoid Receptor Signaling and Pharmacology
脑大麻素受体信号传导和药理学
- 批准号:
6333525 - 财政年份:1997
- 资助金额:
$ 31.98万 - 项目类别:
BRAIN CANNABINOID RECEPTOR SIGNALING AND PHARMACOLOGY
脑大麻素受体信号传导和药理学
- 批准号:
2608215 - 财政年份:1997
- 资助金额:
$ 31.98万 - 项目类别:
BRAIN CANNABINOID RECEPTOR SIGNALING AND PHARMACOLOGY
脑大麻素受体信号传导和药理学
- 批准号:
2837878 - 财政年份:1997
- 资助金额:
$ 31.98万 - 项目类别:
Brain Cannabinoid Receptor Signaling and Pharmacology
脑大麻素受体信号传导和药理学
- 批准号:
6497793 - 财政年份:1997
- 资助金额:
$ 31.98万 - 项目类别:
Brain Cannabinoid Receptor Signaling and Pharmacology
脑大麻素受体信号传导和药理学
- 批准号:
6866454 - 财政年份:1997
- 资助金额:
$ 31.98万 - 项目类别:
Brain Cannabinoid Receptor Signaling and Pharmacology
脑大麻素受体信号传导和药理学
- 批准号:
6628336 - 财政年份:1997
- 资助金额:
$ 31.98万 - 项目类别:
BRAIN CANNABINOID RECEPTOR SIGNALING AND PHARMACOLOGY
脑大麻素受体信号传导和药理学
- 批准号:
2013569 - 财政年份:1997
- 资助金额:
$ 31.98万 - 项目类别:
NGF OR V-SRC DIFFERENTIATED PC12 CELLS--CALCIUM CURRENTS
NGF 或 V-SRC 分化的 PC12 细胞——钙电流
- 批准号:
2267273 - 财政年份:1990
- 资助金额:
$ 31.98万 - 项目类别:
NGF OR V-SRC DIFFERENTIATED PC12 CELLS--CA2+ CURRENTS
NGF 或 V-SRC 分化的 PC12 细胞 - CA2 电流
- 批准号:
3478162 - 财政年份:1990
- 资助金额:
$ 31.98万 - 项目类别:
NGF OR V-SRC DIFFERENTIATED PC12 CELLS--CA2+ CURRENTS
NGF 或 V-SRC 分化的 PC12 细胞 - CA2 电流
- 批准号:
3478163 - 财政年份:1990
- 资助金额:
$ 31.98万 - 项目类别:
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