IONOPHORE A23187: CATION BINDING AND TRANSPORT PROPERTIES *
IONOPHORE A23187: CATION BINDING AND TRANSPORT PROPERTIES *
复制标题
离子载体 A23187：阳离子结合和传输特性 *
DOI：
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发表时间：
1978
期刊：
影响因子：
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通讯作者：
H. Lardy
中科院分区：
文献类型：
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作者：
D. Pfeiffer;Richard W. Taylor;H. Lardy
要理解钙离子作为细胞控制媒介的作用及其生物化学的其他方面，关键要求是能够操纵亚细胞室中阳离子的活性，并在对系统其他性质的干扰最小的情况下特定地改变跨膜钙离子通量。这一领域的一个重要进展是发现了A23187，这是一种二价阳离子选择性离子载体。A23 187大约在五年前上市。自那时以来，已有两千多篇论文发表，其中A23187被用于研究Caz+的代谢及其参与多种组织、细胞的调控机制。和亚细胞细胞器。最近的优秀综述已经涵盖了这些文献的大部分。与其生化特性形成对比，后者得到了深入的研究。对于必须作为这些生化活动基础的，423187的化学知识要有限得多。在本报告中，我们将总结目前已知的这种离子载体的化学和生物物理。在某些领域，这些数据可能看起来很少。我们希望这将强调在解释A23187的生化效应时需要谨慎，并将刺激额外的工作。由于这是议程上唯一一篇关于钙离子载体的论文，我们将首先简要讨论已被提出具有这一活性的其他化合物。另一个被广泛研究的钙离子载体是拉萨洛西德A，以前称为X537A。与A23187一样，拉沙洛西德是一种羧酸，属于聚醚类离子载体(结构见参考文献4)。与A23187的另一个相似之处是它的部分芳香特性。*A23 187和拉沙洛西德经常可以互换使用，得到类似的结果，许多作者从作为钙离子载体的能力角度来解释它的生理活动。然而，现有的化学和生物物理数据表明，拉沙洛西对跨膜钙离子梯度的特定扰动不如A23187有用。它运送一元和三元-
Key requirements in understanding the role of Ca2+ as a cellular control mediator and to other aspects of its biochemistry are the ability to manipulate the activity of the cation in subcellular compartments and to alter specifically transmembrane Ca2+ flux with a minimal disturbance to other properties of the system. An important advance in this area was the discovery of A23 187, a divalent cationselective ionophore. A23 187 became available approximately five years ago.' Since that time over two thousand publications have appeared in which A23187 has been employed to investigate Caz+ metabolism and its.involvement in control mechanisms in a wide variety of tissues, cells. and subcellular organelles. Recent excellent rebiews have covered much of this literature.*J In contrast to its biochemical properties, which have received intensive study. knowledge of the chemistry of ,423187, which must underlie those biochemical activities, is much more limited. In this presentation we will summarize what is currently known of the chemistry and biophysics of this ionophore. The data may seem meager in some areas. We hope this will emphasize the need for caution in interpreting biochemical effects of A23 187 and will stimulate additional work. Since this is the only paper on the agenda devoted to Ca*+ ionophores, we will first discuss briefly other compounds which are known to have been proposed to have this activity. Another widely studied Ca2+ ionophore is lasalocid A. previously called X537A. Like A23187, lasalocid is a carboxylic acid and a member of the polyether class of ionophores (see Reference 4 for structure). A further similarity to A23187 is its partially aromatic character. which distinguishes both ionophores from other members of their cla Lasalocid produces profound physiological effects in a wide variety of systems.* A23 187 and lasalocid may often be used interchangeably with similar results, and many authors have interpreted its physiological activities in terms of an ability to act as a Ca2+ ionophore. However, available chemical and biophysical data indicate that lasalocid is less useful for the specific perturbation of transmembrane Ca2+ gradients than is A23187. It transports monoand tri-