Brain specific non-AT1, non-AT2 angiotensin binding site
脑特异性非 AT1、非 AT2 血管紧张素结合位点
基本信息
- 批准号:8077661
- 负责人:
- 金额:$ 1.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-07-01 至 2012-06-30
- 项目状态:已结题
- 来源:
- 关键词:AGTR2 geneAcidsAddressAffectAffinityAlzheimer&aposs DiseaseAmericanAmino Acid SequenceAmygdaloid structureAngiotensin IIAngiotensin II ReceptorAngiotensin ReceptorAngiotensin Receptor BindingAngiotensinsAnxiety DisordersBasal Nucleus of MeynertBindingBinding ProteinsBinding SitesBiochemicalBiological PreservationBlood PressureBrainBrain IschemiaBrain regionCardiovascular DiseasesCardiovascular systemCause of DeathCaviaCerebrovascular CirculationCharacteristicsComplementCysteineDevelopmentDiseaseDrug abuseElectrolyte BalanceEnzymesFutureGelGene ExpressionGeneticHeart failureHormonesHumanHypertensionImpaired cognitionInfusion proceduresKidneyKnock-outKnowledgeLeadLeftLigandsLightLiquid substanceLiverMediatingMembraneMetabolicMetabolismMiddle Cerebral Artery OcclusionModelingMorbidity - disease rateMotorMovement DisordersMusNerve DegenerationNervous system structureNeuronsNeuropeptidesNucleus AccumbensOryctolagus cuniculusOxidation-ReductionParkinson DiseasePeptide FragmentsPeptide HydrolasesPeptidesPharmaceutical PreparationsPhysiologicalPlayPredispositionProteinsRadiolabeledRat StrainsRattusReactive Oxygen SpeciesReducing AgentsRegulationReportingResearchResearch InfrastructureRodentRoleSiteSpecificitySpinal CordStressStrokeStructureSubstantia GelatinosaSubstantia nigra structureSulfhydryl ReagentsSurveysSystemTechniquesTransgenic MiceUncertaintyWorkabstractingangiotensinasebaseblood pressure regulationchronic paincrosslinkhigh throughput screeninghypertension treatmentinhibitor/antagonistkillingsmetabolic abnormality assessmentneurolysinnormotensivenovelnovel therapeuticspolyacrylamide gelsradiotracerreceptorsalt intakethimet oligopeptidasetreatment strategytwo-dimensional
项目摘要
Project Summary/Abstract
There are many uncertainties about the brain angiotensin system and its functionality is controversial.
However, it is generally accepted that brain angiotensin causes hypertension and other cardiovascular
disorders. With the recognition of functionality of peptide fragments of angiotensin II some having their own
receptors, it is now known that brain angiotensins have a multitude of functions extending well beyond
regulation of the cardiovascular system. We recently discovered a non-AT1, non-AT2 binding site in the brain
that may add an additional layer of complexity to the brain angiotensin system. It is present in higher quantities
than either of the major angiotensin receptor subtypes and could function either as a novel receptor for
angiotensins that may be limited to the brain, or it could be a highly specific angiotensinase that plays a critical
role in the metabolism of angiotensin peptides. To better understand this binding site, this project is directed to
further characterizing this novel, brain-specific non-AT1, non-AT2 binding site for angiotensin peptides. The
first specific aim is to define its biochemical characteristics through polyacrylamide gel purification and
sequencing techniques to determine the amino acid sequence and structure of the binding site. The second
specific aim is to determine its pharmacological specifity to determine if this binding site is specific for
angiotensin peptides or if it has a broader substrate/ligand specificity. The third specific aim will study the
distribution of the binding site in the brain and ascertain whether conditions associated with altered brain
angiotensin system regulation of the cardiovascular system or pathophysiological conditions, e.g., brain
ischemia as in stroke, genetic or experimental hypertension and in transgenic mice lacking angiotensin
receptors, can alter the expression of this binding site in specific brain regions. The changes should enable us
to do a functional neuroanatomical assessment of its possible participation in physiological and
pathophysiological circumstances. It is anticipated that this protein will prove to be of considerable importance
in the functionality of the brain angiotensin system. Since the brain angiotensin system is notorious for causing
cardiovascular disease, this research could lead to the development of novel therapeutic strategies for
treatment of hypertension and stroke. However the occurrence of this binding site in high concentrations in
brain regions such as the nucleus basalis of Meynert, substantia nigra, amygdala, nucleus accumbens and
substantia gelatinosa of the spinal cord could explain the proposed involvement of the brain angiotensins
system in Alzheimer's and Parkinson's Disease, stress and anxiety disorders, drug abuse and chronic pain.
项目总结/摘要
脑血管紧张素系统存在许多不确定性,其功能也存在争议。
然而,普遍认为脑血管紧张素导致高血压和其他心血管疾病,
紊乱随着对血管紧张素II的肽片段的功能性的识别,一些肽片段具有它们自己的功能,
由于血管紧张素受体,现在已知脑血管紧张素具有多种功能,
调节心血管系统。我们最近在大脑中发现了一个非AT 1,非AT 2结合位点,
这可能会给大脑血管紧张素系统增加额外的复杂性。它以更高的量存在
比任何一种主要的血管紧张素受体亚型,可以作为一种新的受体,
血管紧张素可能仅限于大脑,或者它可能是一种高度特异性的血管紧张素酶,
在血管紧张素肽代谢中的作用。为了更好地了解这个绑定网站,这个项目是针对
进一步表征了血管紧张素肽的这种新的脑特异性非AT 1、非AT 2结合位点。的
第一个具体目的是通过聚丙烯酰胺凝胶纯化来确定其生化特性,
测序技术以确定结合位点的氨基酸序列和结构。第二
具体目的是确定其药理学特异性,以确定该结合位点是否特异于
血管紧张素肽或如果它具有更广泛的底物/配体特异性。第三个具体目标将研究
结合位点在脑中的分布,并确定是否与改变的脑
血管紧张素系统调节心血管系统或病理生理状况,例如,大脑
缺血如中风、遗传性或实验性高血压和缺乏血管紧张素Ⅱ的转基因小鼠
受体,可以改变在特定的大脑区域的这种结合位点的表达。这些变化应该能让我们
做一个功能性神经解剖学评估,
病理生理环境。预计这种蛋白质将被证明是相当重要的
大脑血管紧张素系统的功能。因为脑血管紧张素系统是臭名昭著的,
心血管疾病,这项研究可能导致新的治疗策略的发展,
治疗高血压和中风。然而,这种结合位点在高浓度下的出现,
大脑区域,如Meynert基底核、黑质、杏仁核、延髓核和
脊髓胶状质可以解释脑血管紧张素的参与
系统在阿尔茨海默氏症和帕金森氏症,压力和焦虑症,药物滥用和慢性疼痛。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Robert Charles Speth其他文献
Robert Charles Speth的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Robert Charles Speth', 18)}}的其他基金
Development of a radioligand for assay of angiotensin-converting enzyme-2(ACE-2)
开发用于检测血管紧张素转换酶-2(ACE-2)的放射性配体
- 批准号:
8665091 - 财政年份:2013
- 资助金额:
$ 1.56万 - 项目类别:
Development of a radioligand for assay of angiotensin-converting enzyme-2(ACE-2)
开发用于检测血管紧张素转换酶-2(ACE-2)的放射性配体
- 批准号:
8665090 - 财政年份:2013
- 资助金额:
$ 1.56万 - 项目类别:
Development of a radioligand for assay of angiotensin-converting enzyme-2(ACE-2)
开发用于检测血管紧张素转换酶-2(ACE-2)的放射性配体
- 批准号:
8665088 - 财政年份:2013
- 资助金额:
$ 1.56万 - 项目类别:
Development of a radioligand for assay of angiotensin-converting enzyme-2(ACE-2)
开发用于检测血管紧张素转换酶-2(ACE-2)的放射性配体
- 批准号:
8433896 - 财政年份:2013
- 资助金额:
$ 1.56万 - 项目类别:
Brain specific non-AT1, non-AT2 angiotensin binding site
脑特异性非 AT1、非 AT2 血管紧张素结合位点
- 批准号:
8077033 - 财政年份:2009
- 资助金额:
$ 1.56万 - 项目类别:
Brain specific non-AT1, non-AT2 angiotensin binding site
脑特异性非 AT1、非 AT2 血管紧张素结合位点
- 批准号:
7844980 - 财政年份:2009
- 资助金额:
$ 1.56万 - 项目类别:
Brain specific non-AT1, non-AT2 angiotensin binding site
脑特异性非 AT1、非 AT2 血管紧张素结合位点
- 批准号:
8077633 - 财政年份:2009
- 资助金额:
$ 1.56万 - 项目类别:
Brain specific non-AT1, non-AT2 angiotensin binding site
脑特异性非 AT1、非 AT2 血管紧张素结合位点
- 批准号:
8077669 - 财政年份:2009
- 资助金额:
$ 1.56万 - 项目类别:
Brain specific non-AT1, non-AT2 angiotensin binding site
脑特异性非 AT1、非 AT2 血管紧张素结合位点
- 批准号:
8019652 - 财政年份:2009
- 资助金额:
$ 1.56万 - 项目类别:
ANGIOTENSIN II RECEPTORS & OTHER MEMBERS OF G PROTEIN LINKED RECEPTOR FAMILY
血管紧张素 II 受体
- 批准号:
6221113 - 财政年份:1999
- 资助金额:
$ 1.56万 - 项目类别:
相似国自然基金
具有抗癌活性的天然产物金霉酸(Aureolic acids)全合成与选择性构建2-脱氧糖苷键
- 批准号:22007039
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
海洋放线菌来源聚酮类化合物Pteridic acids生物合成机制研究
- 批准号:
- 批准年份:2019
- 资助金额:10.0 万元
- 项目类别:省市级项目
手性Lewis Acids催化的分子内串联1,5-氢迁移/环合反应及其在构建结构多样性手性含氮杂环化合物中的应用
- 批准号:21372217
- 批准年份:2013
- 资助金额:80.0 万元
- 项目类别:面上项目
对空气稳定的新型的有机金属Lewis Acids催化剂制备、表征与应用研究
- 批准号:21172061
- 批准年份:2011
- 资助金额:30.0 万元
- 项目类别:面上项目
钛及含钛Lewis acids促臭氧/过氧化氢体系氧化性能的广普性、高效性及其机制
- 批准号:21176225
- 批准年份:2011
- 资助金额:60.0 万元
- 项目类别:面上项目
基于Zip Nucleic Acids引物对高度降解和低拷贝DNA检材的STR分型研究
- 批准号:81072511
- 批准年份:2010
- 资助金额:31.0 万元
- 项目类别:面上项目
海洋天然产物Makaluvic acids 的全合成及其对南海鱼虱存活的影响
- 批准号:30660215
- 批准年份:2006
- 资助金额:21.0 万元
- 项目类别:地区科学基金项目
相似海外基金
Lipid nanoparticle-mediated Inhalation delivery of anti-viral nucleic acids
脂质纳米颗粒介导的抗病毒核酸的吸入递送
- 批准号:
502577 - 财政年份:2024
- 资助金额:
$ 1.56万 - 项目类别:
CAREER: Highly Rapid and Sensitive Nanomechanoelectrical Detection of Nucleic Acids
职业:高度快速、灵敏的核酸纳米机电检测
- 批准号:
2338857 - 财政年份:2024
- 资助金额:
$ 1.56万 - 项目类别:
Continuing Grant
Double Incorporation of Non-Canonical Amino Acids in an Animal and its Application for Precise and Independent Optical Control of Two Target Genes
动物体内非规范氨基酸的双重掺入及其在两个靶基因精确独立光学控制中的应用
- 批准号:
BB/Y006380/1 - 财政年份:2024
- 资助金额:
$ 1.56万 - 项目类别:
Research Grant
Quantifying L-amino acids in Ryugu to constrain the source of L-amino acids in life on Earth
量化 Ryugu 中的 L-氨基酸以限制地球生命中 L-氨基酸的来源
- 批准号:
24K17112 - 财政年份:2024
- 资助金额:
$ 1.56万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Synthetic analogues based on metabolites of omega-3 fatty acids protect mitochondria in aging hearts
基于 omega-3 脂肪酸代谢物的合成类似物可保护衰老心脏中的线粒体
- 批准号:
477891 - 财政年份:2023
- 资助金额:
$ 1.56万 - 项目类别:
Operating Grants
Metabolomic profiles of responders and non-responders to an omega-3 fatty acids supplementation.
对 omega-3 脂肪酸补充剂有反应和无反应者的代谢组学特征。
- 批准号:
495594 - 财政年份:2023
- 资助金额:
$ 1.56万 - 项目类别:
Molecular recognition and enantioselective reaction of amino acids
氨基酸的分子识别和对映选择性反应
- 批准号:
23K04668 - 财政年份:2023
- 资助金额:
$ 1.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Integrated understanding and manipulation of hypoxic cellular functions by artificial nucleic acids with hypoxia-accumulating properties
具有缺氧累积特性的人工核酸对缺氧细胞功能的综合理解和操纵
- 批准号:
23H02086 - 财政年份:2023
- 资助金额:
$ 1.56万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Basic research toward therapeutic strategies for stress-induced chronic pain with non-natural amino acids
非天然氨基酸治疗应激性慢性疼痛策略的基础研究
- 批准号:
23K06918 - 财政年份:2023
- 资助金额:
$ 1.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular mechanisms how arrestins that modulate localization of glucose transporters are phosphorylated in response to amino acids
调节葡萄糖转运蛋白定位的抑制蛋白如何响应氨基酸而被磷酸化的分子机制
- 批准号:
23K05758 - 财政年份:2023
- 资助金额:
$ 1.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)