Dawson R, Felheim R, Phillips M I
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610.
Eur J Pharmacol. 1993 Aug 24;240(2-3):277-82. doi: 10.1016/0014-2999(93)90909-2.
A series of dopamine receptor agonists and antagonists were tested in a renal epithelial cell line (LLC-PK1) for their ability to alter renal dopamine synthesis and secretion. LLC-PK1 cells were incubated with L-3,4-dihydroxyphenylalanine (L-dopa) (250 microM) in the presence and absence of dopaminergic drugs known to be selective for dopamine receptor subtypes and total dopamine synthesis and dopamine secretion into the media were measured directly by high performance liquid chromatography (HPLC). Both dopamine receptor agonists and antagonist significantly inhibited dopamine secretion from LLC-PK1 cells at concentrations between 10-100 microM. The phenothiazines, chlorpromazine and trifluoperazine, also significantly inhibited aromatic amino acid decarboxylase activity at 100 microM. The mechanism of action for these dopaminergic drugs appeared to involve the inhibition of dopamine secretion from LLC-PK1 cells by direct competition for outward transport by an organic cation transporter. Inhibition of dopamine secretion by these drugs was usually accompanied by significant elevations of the intracellular stores of dopamine. The results of this study suggest that caution should be exhibited in the interpretation of experiments that employ high concentrations of dopamine drugs, in order to account for the potential interaction of these agents with the renal cation transport system.
在一种肾上皮细胞系（LLC-PK1）中测试了一系列多巴胺受体激动剂和拮抗剂改变肾脏多巴胺合成与分泌的能力。将LLC-PK1细胞与L-3,4-二羟基苯丙氨酸（L-多巴）（250微摩尔）一起孵育，分别在存在和不存在已知对多巴胺受体亚型具有选择性的多巴胺能药物的情况下，通过高效液相色谱法（HPLC）直接测量总的多巴胺合成以及释放到培养基中的多巴胺分泌量。多巴胺受体激动剂和拮抗剂在10 - 100微摩尔的浓度下均能显著抑制LLC-PK1细胞的多巴胺分泌。吩噻嗪类药物氯丙嗪和三氟拉嗪在100微摩尔时也能显著抑制芳香族氨基酸脱羧酶的活性。这些多巴胺能药物的作用机制似乎涉及通过与有机阳离子转运体竞争外向转运，直接抑制LLC-PK1细胞的多巴胺分泌。这些药物对多巴胺分泌的抑制通常伴随着细胞内多巴胺储备的显著增加。本研究结果表明，在解释使用高浓度多巴胺药物的实验时应谨慎，以便考虑这些药物与肾脏阳离子转运系统的潜在相互作用。
