Dopamine receptor agonists and antagonists both inhibit dopamine secretion in LLC-PK1 cells

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.