Takahashi M, Sugino H, Kudo Y
Brain Res. 1986 Sep 24;382(2):332-8. doi: 10.1016/0006-8993(86)91342-9.
Monensin, a monovalent cation ionophore, induced profound release of radiolabeled materials from clonal rat pheochromocytoma cells (PC12h) preloaded with [3H]norepinephrine (NE). The release was suppressed in the absence of external Na+, but was not affected at all in the absence of external Ca2+. Cytosolic free Ca2+ concentration ([Ca2+]i), that was monitored by means of a fluorescent Ca2+ indicator, Quin 2, was temporarily increased upon a depolarizing stimulus of high-K+, which induced the Ca2+-dependent release of [3H]NE from PC12h cells. On the other hand, monensin induced only a slight increase in [Ca2+]i. The radiolabeled materials released by high-K+ treatment were mainly [3H]NE, whereas those by monensin were mainly the metabolites of [3H]NE. Pargyline, a monoamine oxidase inhibitor, suppressed both the degradation of [3H]NE stored in PC12h cells and the monensin-induced release of radiolabeled compounds from them. Monensin decreased the content of [3H]NE in storage granules of pargyline-treated cells. Thus, it is likely that monensin expels NE from the storage vesicles to cytosol and then its metabolites by monoamine oxidase are released in a non-exocytotic manner.
莫能菌素是一种单价阳离子离子载体，可促使预先加载了[3H]去甲肾上腺素（NE）的克隆大鼠嗜铬细胞瘤细胞（PC12h）大量释放放射性标记物质。在无细胞外Na+的情况下，这种释放受到抑制，但在无细胞外Ca2+的情况下则完全不受影响。利用荧光Ca2+指示剂喹啉2监测的细胞内游离Ca2+浓度（[Ca2+]i），在高钾去极化刺激时会暂时升高，这种刺激会诱导PC12h细胞中[3H]NE的Ca2+依赖性释放。另一方面，莫能菌素仅使[Ca2+]i略有增加。高钾处理释放的放射性标记物质主要是[3H]NE，而莫能菌素释放的则主要是[3H]NE的代谢产物。单胺氧化酶抑制剂帕吉林既抑制了PC12h细胞中储存的[3H]NE的降解，也抑制了莫能菌素诱导的放射性标记化合物从这些细胞中的释放。莫能菌素降低了经帕吉林处理的细胞储存颗粒中[3H]NE的含量。因此，莫能菌素很可能将NE从储存囊泡排出到细胞质中，然后其代谢产物通过单胺氧化酶以非胞吐方式释放出来。
