The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes.

Tobias Minich, Jan Riemer, Jörg B. Schultz, Pieter Wielinga, Jan Wijnholds, Ralf Dringen

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Astrocytes play an important role in the glutathione (GSH) metabolism of the brain. To test for an involvement of multidrug resistance protein (Mrp) 1 and 5 in the release of GSH and glutathione disulfide (GSSG) from astrocytes, we used astrocyte cultures from wild-type, Mrp1-deficient [Mrp1(-/-)] and Mrp5-deficient [Mrp5(-/-)] mice. During incubation of wild-type or Mrp5(-/-) astrocytes, GSH accumulated in the medium at a rate of about 3 nmol/(, whereas the export of GSH from Mrp1(-/-) astrocytes was only one-third of that. In addition, Mrp1(-/-) astrocytes had a 50% higher specific GSH content than wild-type or Mrp5(-/-) cells. The presence of 50 microm of the Mrp inhibitor MK571 inhibited the rate of GSH release from wild-type and Mrp5(-/-) astrocytes by 60%, but stimulated at the low concentration of 1 microm GSH release by 40%. In contrast, both concentrations of MK571 did not affect GSH export from Mrp1(-/-) astrocytes. Moreover, in contrast to wild-type and Mrp5(-/-) cells, GSSG export during H(2)O(2) stress was not observed for Mrp1(-/-) astrocytes. These data demonstrate that in astrocytes Mrp1 mediates 60% of the GSH export, that Mrp1 is exclusively responsible for GSSG export and that Mrp5 does not contribute to these transport processes.
Original languageEnglish
JournalJournal of Neurochemistry
Pages (from-to)373-384
Publication statusPublished - 2006
Externally publishedYes

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