Capsaicin Receptor Subtypes in Pain Transduction
疼痛传导中的辣椒素受体亚型
基本信息
- 批准号:6730571
- 负责人:
- 金额:$ 28.79万
- 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:1999-04-01 至 2006-03-31
- 项目状态:已结题
- 来源:
- 关键词:SDS polyacrylamide gel electrophoresisXenopus oocyteafferent nervecapsaicindrug receptorsgenetic promoter elementgenetic transcriptiongenomeheat stimulushyperalgesiain situ hybridizationinflammationlaboratory ratlipoxygenasenerve growth factorsneural transmissionneuronsnociceptorspainpolymerase chain reactionprotein structure functionreceptor expressiontissue /cell culturevoltage /patch clampwestern blottings
项目摘要
DESCRIPTION (provided by applicant) Despite intense efforts to effectively
treat acute and chronic pain, current therapies are still associated with
significant side effects including central nervous system depression,
development of tolerance and risk of addiction. Since the majority of acute and
chronic pain is maintained by the persistent activation of specialized sensory
neurons, the selective blockade of pain sensing nerve terminals could represent
a novel way to treat pain with fewer unwanted side effects. Recent advances
have been made in the characterization of receptors and ion channels that
function to detect painful noxious stimuli. Notably, the vanilloid (capsaicin)
receptorVR1 has been isolated and is undergoing intense characterization to
determine whether it can direct sensory nerve activation in response to painful
stimuli. Because the response properties of sensory neurons are complex, we
have investigated whether other related receptor / ion channels exist in
sensory neurons. This effort has revealed the existence of vanilloid receptor
splice variants. VR.5'sv is one such variant that we isolated that appears
insensitive to capsaicin and other noxious stimuli. In this proposal, we are
testing the hypothesis that VR.5'sv can block the activation of VR1 in response
to noxious stimuli when both proteins are expressed together. Another vanilloid
receptor splice variant originally identified in kidney by another laboratory
was found to have mechano-sensitive properties and therefore is termed "stretch
inactivated channel." SIC is activated by cell shrinkage, and based on its
pattern of expression in sensory neurons, it may participate in the detection
of noxious hypertonic conditions. Comparison of SIC to VR1 and VR.5'sv has
revealed a unique structural feature that could help explain its ability to
couple changes in cell shape into channel activation. We propose to study this
feature in the hope to better understand how noxious mechanical stimuli are
detected by sensory neurons. Although our understanding about VR1 and its
splice variants have grown, little is known about what factors control their
abundance in the sensory nerve terminals. Using genomic fragments isolated
upstream from the vanilloid receptor gene and inserted into reporter plasmids,
we will test the hypothesis that tissue derived growth factors positively
regulate the amount of RNA encoding VR1 in sensory neurons through their effect
on RNA transcription. Moreover, using this assay system, we hope to determine
in general what factors regulate VR1, VR.5' sv and SIC. Determining bow these
factors increase or decrease the transcription of VR subtypes will provide a
potential means to modulate pain transduction and hyperalgesia.
描述(由申请人提供)尽管努力有效地
项目成果
期刊论文数量(0)
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{{ truncateString('MARK A SCHUMACHER', 18)}}的其他基金
Capsaicin Receptor Subtypes in Pain Transduction
疼痛传导中的辣椒素受体亚型
- 批准号:
6876643 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
Capsaicin receptor subtypes in pain transduction
疼痛传导中的辣椒素受体亚型
- 批准号:
8109323 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
Capsaicin receptor subtypes in pain transduction
疼痛传导中的辣椒素受体亚型
- 批准号:
8133166 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
Capsaicin receptor subtypes in pain transduction
疼痛传导中的辣椒素受体亚型
- 批准号:
7882324 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
Capsaicin receptor subtypes in pain transduction
疼痛传导中的辣椒素受体亚型
- 批准号:
8312645 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
CAPSAICIN RECEPTOR SUBTYPES IN PAIN TRANSDUCTION
疼痛传导中的辣椒素受体亚型
- 批准号:
6187810 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
Capsaicin Receptor Subtypes in Pain Transduction
疼痛传导中的辣椒素受体亚型
- 批准号:
6620997 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
CAPSAICIN RECEPTOR SUBTYPES IN PAIN TRANSDUCTION
疼痛传导中的辣椒素受体亚型
- 批准号:
2850668 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
CAPSAICIN RECEPTOR SUBTYPES IN PAIN TRANSDUCTION
疼痛传导中的辣椒素受体亚型
- 批准号:
6394145 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
Capsaicin Receptor Subtypes in Pain Transduction
疼痛传导中的辣椒素受体亚型
- 批准号:
6429955 - 财政年份:1999
- 资助金额:
$ 28.79万 - 项目类别:
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