Abstract.
Incubation of PC12 cells with the sulfonylurea drug, glipizide (1–100 µM), increased intracellular levels of the acidic metabolites of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The levels of these acids in the medium were decreased, indicating the presence of a sulfonylurea-sensitive organic anion transporter. In the present study, we demonstrate that the sulfonylurea-sensitive transport of acidic dopamine metabolites is unidirectional, ATP dependent, unaffected by ouabain or by tetrodotoxin and blocked by drugs that interact with the multidrug-resistance protein-1 (MRP1). However, over-expression of MRP1 did not affect transport of the acid metabolites. The pharmacological profile and ion dependence of the transporter also differs from that of known ATP-binding cassette (ABC) family members. Using microdialysis, we also demonstrated a sulfonylurea-sensitive transport process in the striatum of freely moving rats. These results show that acidic dopamine metabolites are actively secreted from dopaminergic cells into surrounding extracellular fluid by a previously undescribed transporter.
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Lamensdorf, I., Hrycyna, C., He, LP. et al. Acidic dopamine metabolites are actively extruded from PC12 cells by a novel sulfonylurea-sensitive transporter. Naunyn-Schmied Arch Pharmacol 361, 654–664 (2000). https://doi.org/10.1007/s002100000246
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DOI: https://doi.org/10.1007/s002100000246