PERIVASCULAR CA+ RECEPTOR--THERAPEUTIC SIGNIFICANCE

血管周围CA受体--治疗意义

• 批准号: 2522636
• 负责人: Richard D Bukoski
• 金额: $ 10万
• 依托单位: NPS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2522636
• 关键词: RNA splicing; antihypertensive agents; blood pressure; calcium ion; cardiovascular pharmacology; denervation; laboratory rat; molecular cloning; parathyroid gland; receptor; receptor expression; tissue /cell culture; vascular smooth muscle nervous control; vasodilators

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.

描述(改编自申请者摘要)：长期目标 该建议是在开发抗高血压药物的前提下提出的 甲状旁腺钙受体(CAR)的一种独特形式存在于 血管周围神经和该受体的刺激导致 血管扩张剂的精制。初步数据显示， 汽车可能是一种参与血液调节的感官 压力。申请人提出了几条证据来支持 他关于汽车可能是调节血管的关键因素的假说 语气。 在目标1中，将测试一个假设，该假设表明慢性或急性 去血管周围神经导致血管周围血管减少 细胞外钙离子诱导的血管张力的表达和降低。 在这样的研究中，去神经将通过两种方式和 将使用申请者常规使用的生理学方法。 研究血管张力的变化。在《目标2》中，有趣的是 甲状旁腺钙剪接的明显变化观察 神经中的受体将通过5‘-RACE、cdna克隆和 CDNAs表达。 建议的商业应用： 这笔赠款的目标和相关的商业应用是 确定使用血管周围感觉神经钙离子的可行性 以受体为靶点的药物设计可作为 抗高血压血管扩张剂对盐敏感的疗效增加 高血压患者，包括老年和少数民族人群。