Efflux of glutathione conjugate of monochlorobimane from striatal and cortical neurons

Evidence for the presence of a novel transporter in primary cultures of rat striatal neurons and mouse cortical neurons similar in function to the mul tidrug resistance-associated protein (MRP1) is presented. Functional activi ty was assessed by efflux studies with the glutathione conjugate of monochl orobimane (B-SG). The glutathione transferase-catalyzed formation of B-SG i n rat striatal neurons and mouse cortical neurons was inhibited by ethacryn ic acid. The efflux of B-SG from rat striatal neurons and mouse cortical ne urons was lower at 20 degreesC than at 37 degreesC and was lower in cells w ith reduced ATP concentrations compared with cells with constitutive ATP co ncentrations. In addition, the efflux of B-SG was inhibited by MK-571 in bo th rat striatal and mouse cortical neurons and by probenecid in rat striata l neurons, but not in mouse cortical neurons. Verapamil did not inhibit B-S G efflux in either rat striatal or mouse cortical neurons. Although functio nally similar to MRP1, Western blot analysis with commercially available an tibodies directed against human and mouse MRP1 failed to show MRP1-like pro tein in either whole-cell homogenates of rat striatal neurons or mouse cort ical neurons, indicating that the described neuronal transporter differs in structure from human or mouse MRP1 or lacks epitopes in common with MRP1.