BIOLOGY OF INOPHORES: A STRUCTURE/REACTIVITY STUDY

建议研究一系列自然发生的和 合成离子载体对右心房自发搏动的影响 白色新西兰兔的起搏区。 两类离子载体 已被证明具有作为抗高血压药物的潜力， 血管扩张剂，以增强血液流动，并因此，例如，受损的心脏 肌肉收缩力 尽管有这种潜力，但关于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， 负责肌肉紧张和活动的发展。 的 一项提议的研究包括详细使用已知金属离子的离子载体 特异性，以修改肌肉张力和跳动率的 心房区 通过观察离子选择性物质的作用， 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功能甚至不是微不足道的 与我们对他们的实验室物理知识相比， 化学性质，包括金属离子在疏水介质中的传输 液膜 来自拟议系统的初步数据 说明了计划研究的可行性。 最初的研究将使用这样的离子特异性离子载体， 莫能菌素（Na）、缬氨霉素（K）和X-537 A（Ca），以确定 干扰这些离子在心房区域上的通量。 其中一些 化合物以前曾在其他实验室进行过研究，但最初 在我们的实验室重复，再加上其他离子载体将 提供一个更好的程序来评估我们的结果。 其他离子载体 研究包括各种冠和隐窝，也是一系列新的 化合物，硅冠醚，已被证明具有离子亲 性格，没有一些潜在的讨厌的副作用报告， 规则冠和穴离子载体。 在我们研究的同时， 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。

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.