cGMP transport by vesicles from human and mouse erythrocytes

Cornelia J.F. De Wolf, Hiroaki Yamaguchi, Ingrid Van Der Heijden, Peter R. Wielinga, Stefanie L. Hundscheid, Nobuhito Ono, George L. Scheffer, Marcel De Haas, John D. Schuetz, Jan Wijnholds, Piet Borst

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

cGMP secretion from cells can be mediated by ATP-binding cassette (ABC) transporters ABCC4, ABCC5, and ABCC11. Indirect evidence suggests that ABCC4 and ABCC5 contribute to cGMP transport by erythrocytes. We have re-investigated the issue using erythrocytes from wild-type and transporter knockout mice. Murine wild-type erythrocyte vesicles transported cGMP with an apparent Km that was 100-fold higher than their human counterparts, the apparent V max being similar. Whereas cGMP transport into human vesicles was efficiently inhibited by the ABCC4-specific substrate prostaglandin E 1, cGMP transport into mouse vesicles was inhibited equally by Abcg2 and Abcc4 inhibitors/substrates. Similarly, cGMP transport into vesicles from Abcc4-/- and Abcg2-/- mice was 42% and 51% of that into wild-type mouse vesicles, respectively, whereas cGMP transport into vesicles from Abcc4-/-/Abcg2-/- mice was near background. The knockout mice were used to show that Abcg2-mediated cGMP transport occurred with lower affinity but higher Vmax than Abcc4-mediated transport. Involvement of Abcg2 in cGMP transport by Abcc4-/- erythrocyte vesicles was supported by higher transport at pH 5.5 than at pH 7.4, a characteristic of Abcg2-mediated transport. The relative contribution of ABCC4/Abcc4 and ABCG2/Abcg2 in cGMP transport was confirmed with a new inhibitor of ABCC4 transport, the protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride.

Original languageEnglish
Pages (from-to)439-450
Number of pages12
JournalFEBS Journal
Volume274
Issue number2
DOIs
Publication statusPublished - 2007 Jan

Keywords

  • ABCC4
  • ABCG2
  • Multidrug resistance
  • Multidrug resistance protein (MRP)
  • cGMP

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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