PERIVASCULAR CA+ RECEPTOR--THERAPEUTIC SIGNIFICANCE

描述（改编自申请人的摘要）：长期目标 该建议是在开发抗高血压药物的前提下， 甲状旁腺Ca 2+受体（CaR）的独特形式存在于 血管周围神经，刺激这种受体会导致 血管扩张物质的加工。 初步数据表明 CaR可能是一种参与血液调节的感觉器官， 压力 申请人提出了几条证据来支持 他的假设是，CaR可能是调节血管生成的关键因素， 语气 在目标1中，将检验一个假设，即慢性或急性 血管周围去神经导致血管周围CaR减少 表达和细胞外Ca 2+诱导的血管张力降低。 在这些研究中，将通过两种方式诱导去神经， 将使用申请人常规使用的生理学方法 来研究血管张力的变化 在目标2中， 观察到甲状旁腺钙剪接的明显变化 将通过5 '-RACE、cDNA克隆和 cDNA表达。 拟定商业应用： 该补助金的目标和相关的商业应用是 确定使用血管周围感觉神经Ca 2 + 受体作为设计药物的靶点， 对盐敏感性患者具有增强功效的抗高血压血管扩张剂 高血压患者，包括老年人和少数民族人群。

DESCRIPTION (Adapted from applicant's abstract): The long term goal of the proposal is to develop anti-hypertension drugs based on the premise that a distinct form of the parathyroid Ca2+ receptor (CaR) exists in perivascular nerves and that stimulation of this receptor leads to elaboration of a vasodilator substance. Preliminary data indicate that the CaR may be a sensory that is involved in the regulation of blood pressure. The applicant advances several lines of evidence to support his hypothesis that the CaR may be a key element in modulating vascular tone. In aim 1, a hypothesis will be tested which states that chronic or acute perivascular denervation results in reduction in perivascular CaR expression and a reduction in extracellular Ca2+ induced vascular tone. In such studies, denervation will be induced by two means and physiological methods, employed routinely by the applicant, will be used to study alterations in vascular tone. In aim 2, the interesting observation of an apparent change in splicing of the parathyroid calcium receptor in nerve will be investigated by 5'-RACE, cDNA cloning, and cDNA expression. PROPOSED COMMERCIAL APPLICATION: The goal and associated commercial application of this grant is to determine the feasibility of using the perivascular sensory nerve Ca2+ receptor as a target for the design of drugs that can be used as antihypertensive vasodilators with increased efficacy for salt sensitive hypertensive patients, including aged and minority populations.