Bennett J P, Cockcroft S, Gomperts B D
Nature. 1979;282(5741):851-3. doi: 10.1038/282851a0.
The activation of cellular function following the direct introduction of Ca2+ into the cytosol by the use of a Ca2+-transporting ionophore has served to confirm the widely held idea that Ca2+ has the status of a second messenger in many cell types. However, this evidence has been obtained largely from the use of a single ionophore, the antibiotic A23187; experiments with X537A, which is another ionophorous antibiotic capable of transporting Ca2+ (ref. 3), have failed to show the expected characteristics. For example, histamine release from rat mast cells mediated by X537A is neither dependent on extracellular Ca2+ nor prevented by metabolic inhibitors. Ionomycin is a recently described polyether antibiotic produced by Streptomyces conglobatus ATCC 31005, and is active against Gram-positive bacteria. The antibiotic action is presumably due to its ionophorous properties, as it extracts Ca2+ from an aqueous phase into an organic phase with a stoichiometry of 1:1 (ref. 6). The ionophore is also capable of transporting 45Ca2+ across biological membranes (our unpublished results). Here we report the application of ionomycin to rat mast cells. We show that ionomycin stimulates mast cell secretion solely through its ability to form a lipid-soluble calcium complex, and thus to convey Ca2+ across the hydrocarbon region of the cell membrane.
通过使用钙离子转运离子载体将Ca2+直接导入细胞质溶胶后细胞功能的激活，证实了一种广泛持有的观点，即Ca2+在许多细胞类型中具有第二信使的地位。然而，这一证据主要来自于使用单一离子载体——抗生素A23187；而使用另一种能够转运Ca2+的离子载体抗生素X537A进行的实验（参考文献3），却未能显示出预期的特征。例如，由X537A介导的大鼠肥大细胞组胺释放既不依赖细胞外Ca2+，也不受代谢抑制剂的抑制。离子霉素是最近描述的一种由球状链霉菌ATCC 31005产生的聚醚抗生素，对革兰氏阳性菌有活性。其抗菌作用可能归因于其离子载体特性，因为它能以1:1的化学计量比将Ca2+从水相提取到有机相（参考文献6）。该离子载体还能够携带45Ca2+穿过生物膜（我们未发表的结果）。在此，我们报告离子霉素在大鼠肥大细胞中的应用。我们发现，离子霉素仅通过其形成脂溶性钙复合物的能力来刺激肥大细胞分泌，从而将Ca2+转运穿过细胞膜的碳氢区域。
