Acidic dopamine metabolites are actively extruded from PC12 cells by a novel sulfonylurea-sensitive transporter

Incubation of PC 12 cells with the sulfonylurea drug. glipizide (1-100 mu M ), increased intracellular levels of the acidic metabolites of dopamine, 3, 4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA). The leve ls of these acids in the medium were decreased, indicating the presence of a sulfonylurea-sensitive organic anion transporter. In the present study, w e demonstrate that the sulfonylurea-sensitive transport of acidic dopamine metabolites is unidirectional, ATP dependent, unaffected by ouabain or by t etrodotoxin and blocked by drugs that interact with the multidrug-resistanc e protein-1 (MRP1). However, over-expression of MRP1 did not affect transpo rt of the acid metabolites. The pharmacological profile and ion dependence of the transporter also differs from that of known ATP binding cassette (AB C) family members. Using microdialysis, we also demonstrated a sulfonylurea -sensitive transport process in the striatum of freely moving rats. These r esults show that acidic dopamine metabolites an actively secreted from dopa minergic cells into surrounding extracellular fluid by a previously undescr ibed transporter.