NMDA Receptor Function in the Kidney

肾脏中 NMDA 受体的功能

• 批准号: 6801458
• 负责人: Karen A Munger
• 金额: $ 26.61万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6801458
• 关键词: NMDA receptors; aminoacid; angiotensins; calcium channel; dietary proteins; high performance liquid chromatography; hypertrophy; immunocytochemistry; kidney circulation; kidney function; laboratory rat; neurotransmitter antagonist; nitric oxide; northern blottings; polyamines; polymerase chain reaction; posttranslational modifications; protein structure function; receptor expression; western blottings

DESCRIPTION (provided by applicant): We have recently discovered the presence of the N-rnethyI-D-aspartate (NMDA) receptorin the rat kidney. This receptor functions as a calcium channel and has been extensively examined in the brain. Studies proposed in this application will test the Hypothesis that: The NMDA receptor has an important functional role in the kidney, which is independent from its central nervous action as an amino acid neurotransmitter receptor. To test this hypothesis, the following Specific Aims will be addressed. 1) Characterization and localization of the NMDA receptors in the kidney. By using immunohistochemical localization, Western blot analysis, Northern blot and RT-PCR techniques, we will characterize the NMDA receptor(s) present in the rat kidney. By determining the specific sub-type and location of the receptor, we can make inferences on its possible function(s). 2) Activation of the NMDA receptor and regulation of function in the kidney. Using NMDA receptor antagonists and agonists in the rat, we will evaluate changes in renal function such as renal hemodynamics, sodium and amino acid handling. In addition, by using cultured cell lines and primary cultures, we will examine receptor regulation and function at the cellular level. These studies will determine the baseline function of the NMDA receptor, and provide evidence on possible endogenous agonists of NMDA in the kidney. 3) Physiologic regulation and control of the NMDA receptor in the kidney. These studies will utilize whole animal physiology, and cellular and molecular techniques. We will measure the effects of dietary protein and amino acid manipulations nitricoxide/angiotensin system contributions, hypertrophy and contribution of polyamines to the renal NMDA receptor(s). These studies will determine how the NMDA receptor may be regulated and contribute to the long-term regulation of renal function.These studies will provide valuable information regarding the basic biology of this calcium channel in the kidney and may lead to treatment of renal diseases that are influenced by actions of the NMDA receptor.

描述（由申请人提供）：我们最近发现了大鼠肾脏的N-Rnethyi-d-d-Appartate（NMDA）受体的存在。 该受体充当钙通道，并在大脑中进行了广泛的检查。在本应用中提出的研究将检验以下假设：NMDA受体在肾脏中具有重要的功能作用，该肾脏独立于其作为氨基酸神经递质受体的中枢神经作用。 为了检验这一假设，将解决以下具体目标。 1）NMDA受体在肾脏中的表征和定位。通过使用免疫组织化学定位，蛋白质印迹分析，北印迹和RT-PCR技术，我们将表征大鼠肾脏中存在的NMDA受体。通过确定受体的特定子类型和位置，我们可以推断出其可能的功能。 2）激活NMDA受体和肾脏功能的调节。 使用大鼠中的NMDA受体拮抗剂和激动剂，我们将评估肾功能的变化，例如肾脏血液动力学，钠和氨基酸处理。另外，通过使用培养的细胞系和原代培养物，我们将检查受体调节和功能在细胞水平上。这些研究将确定NMDA受体的基线功能，并提供有关NMDA可能内源性激动剂的证据。 3）肾脏中NMDA受体的生理调节和控制。 这些研究将利用整个动物生理学以及细胞和分子技术。我们将衡量饮食蛋白和氨基酸操纵硝酸/血管紧张素系统的贡献，肥大以及多胺对肾脏NMDA受体的贡献（S）。这些研究将确定如何调节NMDA受体，并为肾功能的长期调节做出贡献。这些研究将提供有关该钙通道在肾脏中基本生物学的宝贵信息，并可能导致受NMDA受体作用影响的肾脏疾病的治疗。