DOPAMINE-RECEPTOR AGONISTS AND ANTAGONISTS BOTH INHIBIT DOPAMINE SECRETION IN LLC-PK(1) CELLS

A series of dopamine receptor agonists and antagonists were tested in a renal epithelial cell line (LLC-PK1) for their ability to alter rena l dopamine synthesis and secretion. LLC-PK1 cells were incubated with L-3,4-dihydroxyphenylalanine (L-dopa) (250 muM) in the presence and ab sence of dopaminergic drugs known to be selective for dopamine recepto r subtypes and total dopamine synthesis and dopamine secretion into th e media were measured directly by high performance liquid chromatograp hy (HPLC). Both dopamine receptor agonists and antagonists significant ly inhibited dopamine secretion from LLC-PK1 cells at concentrations b etween 10-100 muM. The phenothiazines, chlorpromazine and trifluoperaz ine, also significantly inhibited aromatic amino acid decarboxylase ac tivity at 100 muM. The mechanism of action for these dopaminergic drug s appeared to involve the inhibition of dopamine secretion from LLC-PK 1 cells by direct competition for outward transport by an organic cati on transporter. Inhibition of dopamine secretion by these drugs was us ually accompanied by significant elevations of the intracellular store s of dopamine. The results of this study suggest that caution should b e exhibited in the interpretation of experiments that employ high conc entrations of dopamine drugs, in order to account for the potential in teraction of these agents with the renal cation transport system.