Perlman R L, Cossi A F, Role L W
J Pharmacol Exp Ther. 1980 May;213(2):241-6.
A number of carboxylic ionophores stimulate the secretion of norepinephrine from cell suspensions prepared from a transplantable rat pheochromocytoma. The divalent-cation ionophore ionomycin stimulates catecholamine secretion by a mechanism that is dependent upon the presence of extracellular Ca++. It is likely that ionomycin-induced catecholamine secretion results from the ionophore-mediated entry of Ca++ into the cells. The monovalent-cation ionophore monensin stimulates catecholamine secretion by a mechanism that is independent of extracellular Ca++, but is markedly dependent upon extracellular Na+. Monensin probably transports Na+ into the pheochromocytoma cells and increases the intracellular concentration of Na+ in these cells. This rise in intracellular Na+ may cause the release of Ca++ from some intracellular store. Lasalocid stimulates catecholamine secretion by a mechanism that is independent of extracellular Ca++ and is only slightly dependent upon extracellular Na+. The action of lasalocid, in contrast to the actions of ionomycin and monensin, is potentiated by decreased pH. It is likely that lasalocid enters the cells in its uncharged, protonated form. Once inside the cells, lasalocid may promote the release of intracellular Ca++. Alternatively, lasalocid and monensin may stimulate catecholamine secretion by the process which is independent of Ca++. These experiments show that ionophores can stimulate catecholamine secretion by at least three distinct ionic mechanisms.
一些羧酸离子载体可刺激从可移植大鼠嗜铬细胞瘤制备的细胞悬液中去甲肾上腺素的分泌。二价阳离子离子载体离子霉素通过一种依赖于细胞外Ca++存在的机制刺激儿茶酚胺分泌。离子霉素诱导的儿茶酚胺分泌可能是由于离子载体介导的Ca++进入细胞所致。单价阳离子离子载体莫能菌素通过一种不依赖于细胞外Ca++，但明显依赖于细胞外Na+的机制刺激儿茶酚胺分泌。莫能菌素可能将Na+转运到嗜铬细胞瘤细胞中，并增加这些细胞内的Na+浓度。细胞内Na+的这种升高可能导致Ca++从某些细胞内储存库中释放出来。拉沙洛西通过一种不依赖于细胞外Ca++且仅轻微依赖于细胞外Na+的机制刺激儿茶酚胺分泌。与离子霉素和莫能菌素的作用相反，拉沙洛西的作用在pH降低时增强。拉沙洛西可能以不带电荷的质子化形式进入细胞。一旦进入细胞，拉沙洛西可能促进细胞内Ca++的释放。或者，拉沙洛西和莫能菌素可能通过不依赖于Ca++的过程刺激儿茶酚胺分泌。这些实验表明，离子载体可通过至少三种不同的离子机制刺激儿茶酚胺分泌。
