CARDIOVASCULAR AND MOLECULAR PROPERTIES OF IONOPHORES

离子载体的心血管和分子特性

基本信息

批准号：
3337451
负责人：
BERTON C PRESSMAN
金额：
$ 18.95万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-04-01 至 1988-03-31
项目状态：
已结题

项目摘要

The broad objective of this proposal is to understand how the ability of carboxylic ionophores to carry cations across biological membranes interacts with the inherent regulatory processes of cells to produce the resulting biological responses. The effects of ionophores on the heart will be examined at three levels of integration: (1) the responses of conscious dogs deduced from analysis of the aortic pressure wave and blood chemistry; (2) the metabolic and contract-tile responses of the perfused rabbit heart which might provide insight into the remarkable inonophore-induced increased in work efficiency in this preparation as well as intact animals; (3) the contractile responses of culture beating heart cells and their correlation with intracellular calcium activity as reported by the fluorescent probe Quin-2. The responses of heart cells will be compared to the passive responses of RBCs and the responses of cultured lymphoma cells which are induced to "cap" by antigens in a calcium related, ionophore-enhanced process. The general hypothesis that the mechanism by which ionophores influence the metabolic and physiological behavior of cells is by directly increasing intracellular sodium activity thereby promoting a secondary rise in intracellular activity, will be evaluated. The observed interaction of ionophores with phospholipids, which may greatly affect their behavior in biological membranes, will also be characterized. The molecular properties of ionophores underlying their ability to transport cations, i.e. formation of lipid soluble cation complexes, will be studied by circular dichroism (CD), HPLC chromatographic behavior and interaction with the fluorescent cation thallous (T1+). In toto, the information gathered will help determine the therapeutic potential of ionophores for heart failure and shock, as well as their toxic potential for man and animals resulting from the widespread use of ionophores as feed supplements for raising poultry and cattle. This latter consideration will also be pursued by refinement of a novel sensitive assay for ionophores in tissues based directly on their ability to complex cations.

该提议的广泛目标是了解羧基离子载体可在生物膜上携带阳离子与细胞的固有调节过程相互作用，以产生产生的生物反应。离子载体对心脏的影响将在三个级别的集成级别进行检查：（1）从分析主动脉压力波和血液中得出的有意识的狗化学; （2）灌注的代谢和合同反应兔子的心可能会洞悉非凡的无单组引起的工作效率也提高了此准备工作作为完整的动物；（3）文化跳动心脏的收缩反应细胞及其与细胞内钙活性的相关性通过荧光探针quin-2。心脏细胞的反应将是与RBC的被动反应和培养的反应相比在钙相关的抗原中诱导抗原“ CAP”的淋巴瘤细胞，离子载体增强过程。一般假设是哪些离子载有影响的新陈代谢和生理行为细胞是直接增加细胞内钠活性将评估促进细胞内活性的继发性上升。观察到的离子载体与磷脂的相互作用，这可能极大地影响了它们在生物膜中的行为，也将是特征。离子载体的分子特性，其能力的能力运输阳离子，即脂溶性阳离子复合物的形成，将可以通过圆形二色性（CD），HPLC色谱行为和与荧光阳离子thallous（T1+）的相互作用。在Toto中收集的信息将有助于确定心力衰竭和冲击的离子载体及其有毒电位对于由于广泛使用离子载作为饲料而导致的人和动物饲养家禽和牛的补品。后一个考虑将同样可以通过对新型离子载体的敏感测定法的细化来追求组织直接基于其复杂阳离子的能力。