BIOLOGY OF INOPHORES: A STRUCTURE/REACTIVITY STUDY

INOHORES 的生物学：结构/反应性研究

• 批准号: 3439961
• 负责人: KEITH H PANNELL
• 金额: $ 6.72万
• 依托单位: UNIVERSITY OF TEXAS EL PASO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-30 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3439961
• 关键词: atrium; chemical structure function; heart pacemaker tissue; hydropathy; ionophores; membrane permeability; muscle contraction; vascular smooth muscle

It is proposed to study the effect of a series of naturally occurring and synthetic ionophores upon the spontaneous beating of the right atrial pacemaker region of White New Zealand rabbits. Both classes of ionophore have been shown to have potential as antihypertensive drugs and also as vasodilators to enhance blood flow and hence, for example, impaired cardiac muscle contractility. Despite this potential, there are only very limited studies on the effect that these ion carriers have upon the ionic transport mechanisms that are responsible for the development of muscle tension and activity. The research proposed involves a detailed use of ionophores of known metal ion specificity to modify both the muscle tension and beating rate of the atrial region. By observing the effect of ion selective species it will be possible to help in the design of ionophoric materials, since to date the features that control any physiologic activity are not even marginally recognized as compared to our knowledge of their laboratory physical chemical properties, including transport of metal ions across hydrophobic liquid membranes. Preliminary data from the proposed system has illustrated the feasibility of the planned research. Initial studies will be with the use of such ion specific ionophores as monensin (Na), valinomycin (K) and X-537A (Ca) to ascertain the effect of disturbing the flux of these ions upon the atrial region. Some of these compounds have been previously studied in other laboratories, but initial repetition in our laboratory, coupled with the other ionophores will provide a better procedure for evaluating our results. Other ionophores to be studied include various crowns and crypts, and also the new series of compounds, the silacrowns, which have been shown to possess ionophoric character, without some of potentially nasty side effects reported for regular crown and crypt ionophores. In parallel with our studies, ionophore samples will be provided other research groups for testing on vascular smooth muscle preparations.

建议研究一系列自然发生和 右心房自发搏动时的合成离子载体 新西兰白兔的起搏器区域。 两类离子载体 已被证明具有作为抗高血压药物的潜力，也可作为 血管扩张剂可增强血流量，从而增强心脏功能 肌肉收缩力。 尽管有这种潜力，但对其影响的研究非常有限 这些离子载体对离子传输机制的影响是 负责肌肉张力和活动的发展。 这 拟议的研究涉及已知金属离子的离子载体的详细使用 特异性地改变肌肉张力和跳动率 心房区域。 通过观察离子选择性物质的影响， 可能有助于离子载体材料的设计，因为迄今为止 控制任何生理活动的特征甚至都不是微不足道的 与我们对他们实验室物理知识的了解相比，我们得到了认可 化学性质，包括金属离子穿过疏水性的传输 液膜。 拟议系统的初步数据 说明了计划研究的可行性。 初步研究将使用此类离子特异性离子载体，例如 莫能菌素 (Na)、缬氨霉素 (K) 和 X-537A (Ca) 以确定效果 干扰这些离子在心房区域的通量。 其中一些 此前其他实验室已对化合物进行过研究，但最初 在我们的实验室重复，再加上其他离子载体将 提供更好的程序来评估我们的结果。 其他离子载体 所研究的包括各种冠和隐窝，以及新系列 硅冠化合物，已被证明具有离子载体 性格，没有一些潜在的令人讨厌的副作用报告 常规冠和隐窝离子载体。 在我们学习的同时， 离子载体样品将提供给其他研究小组进行测试 血管平滑肌制剂。