Fischer P, Burger A, Graefe K H, Trendelenburg U
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):79-84. doi: 10.1007/BF00165130.
Possible effects of (+/-)-dobutamine on adrenergic nerve endings were determined in experiments with ghosts of bovine chromaffin granules, with rat phaeochromocytoma (PC-12) cells and with the rat vas deferens. Dobutamine inhibited the vesicular uptake of a mixture of 70% adrenaline + 30% 3H-noradrenaline into ghosts, with an IC50 of 1.7 mumol/l. Dobutamine inhibited uptake1 of 3H-noradrenaline in PC-12 cells (with an IC50 of 0.38 mumol/l) without being a substrate. However, dobutamine easily entered PC-12 cells by diffusion. After inhibition of MAO, COMT and vesicular uptake dobutamine (15 and 45 mumol/l) released tritium from rat vasa deferentia preloaded with 3H-noradrenaline. Equi-inhibitory concentrations of dobutamine and desipramine (against uptake1) were equi-releasing. On the other hand, when MAO and vesicular uptake were intact, dobutamine (15 mumol/l) increased the efflux of tritium from preloaded vasa deferentia much more than did an equi-inhibitory concentration of desipramine. Most of the released tritium was then 3H-DOPEG. Dobutamine is a potent inhibitor of uptake1 as well as of vesicular uptake; moreover, it easily diffuses into adrenergic nerve endings. Hence, it blocks the neuronal and the vesicular re-uptake of noradrenaline; consequently, when MAO and vesicular uptake are intact, dobutamine increases the net leakage of noradrenaline from the storage vesicles, thereby leading to an efflux of deaminated metabolites. However, dobutamine is virtually unable to release noradrenaline into the extracellular space.
通过使用牛嗜铬粒蛋白颗粒膜泡、大鼠嗜铬细胞瘤（PC - 12）细胞以及大鼠输精管进行实验，确定了（±）-多巴酚丁胺对肾上腺素能神经末梢可能产生的影响。多巴酚丁胺抑制了70%肾上腺素 + 30% 3H - 去甲肾上腺素混合物进入膜泡的摄取，IC50为1.7 μmol/L。多巴酚丁胺抑制PC - 12细胞中3H - 去甲肾上腺素的摄取1（IC50为0.38 μmol/L），但它不是摄取底物。然而，多巴酚丁胺可通过扩散轻易进入PC - 12细胞。在抑制单胺氧化酶（MAO）、儿茶酚 - O - 甲基转移酶（COMT）和囊泡摄取后，多巴酚丁胺（15和45 μmol/L）使预先装载3H - 去甲肾上腺素的大鼠输精管释放出氚。多巴酚丁胺和地昔帕明（针对摄取1）的等效抑制浓度具有等效释放作用。另一方面，当MAO和囊泡摄取完整时，多巴酚丁胺（15 μmol/L）比等效抑制浓度的地昔帕明更能增加预先装载的输精管中氚的外流。释放出的大部分氚随后是3H - 多巴胺 - O - 硫酸酯（3H - DOPEG）。多巴酚丁胺是摄取1以及囊泡摄取的强效抑制剂；此外，它很容易扩散到肾上腺素能神经末梢。因此，它阻断了去甲肾上腺素的神经元摄取和囊泡摄取；所以，当MAO和囊泡摄取完整时，多巴酚丁胺会增加去甲肾上腺素从储存囊泡的净泄漏，从而导致脱氨基代谢产物的外流。然而，多巴酚丁胺实际上无法将去甲肾上腺素释放到细胞外空间。
