BIOLOGY OF INOPHORES: A STRUCTURE/REACTIVITY STUDY

有人建议研究一系列自然发生的和 人工合成离子载体对右房自发搏动的影响 新西兰大白兔的起搏区。这两类离子载体 已经被证明具有作为降压药的潜力，也被证明是 血管扩张剂，以增加血液流动，从而，例如，损害心脏 肌肉的收缩能力。 尽管有这种潜力，但关于这种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 负责发展肌肉的张力和活跃度。这个 建议的研究涉及已知金属离子的电离团的详细使用 改变肌肉张力和搏动频率的特异性 心房区域。通过观察离子选择性物种的影响，它将是 可能有助于电离辐射材料的设计，因为到目前为止 控制任何生理活动的特征甚至都不是 与我们对他们实验室物理知识的认识相比较 化学性质，包括金属离子通过疏水的传输 液膜。来自拟议系统的初步数据已 说明了计划研究的可行性。 初步研究将使用离子特定的离子载体，如 莫能菌素(Na)、呋喃霉素(K)和X-537A(Ca)的作用 干扰这些离子在心房区的流量。其中一些 化合物以前也曾在其他实验室进行过研究，但最初 在我们实验室的重复实验，再加上其他的电离团 为评估我们的结果提供更好的程序。其他电离团 正在研究的包括各种王冠和地穴，以及新的系列 化合物，硅冠，已被证明具有离子转运体 性格，没有一些潜在的不良副作用报道 常规的皇冠和地穴离子载体。在我们学习的同时， 离子浮体样本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.