Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein.

摘要: Sister of P-glycoprotein (SPGP), a novel murine cDNA and member the ATP-binding cassette superfamily highly homologous to (Pgp), was cloned. Moreover, its genomic clone isolated localized chromosome 2 by fluorescence in situ hybridization. SPGP functionally evaluated relative MDR1 after subcloning into retroviral bicistronic vector capable expressing both green fluorescent protein. LLC-PK1 MDCKII cells were transduced with this retrovirus SPGP-positive clones isolated. Drug uptake efflux compared ectopically either or human MDR1. had decreased taurocholate vinblastine cells. Additional studies revealed that accelerated LLC-PK1. Further comparison although easily impaired vincristine, daunomycin, paclitaxel, digoxin, no effect on these drugs. However, further demonstrated that, like MDR1, effluxed calcein-acetoxymethyl ester (AM). Unlike incapable effluxing rhodamine 123. Although cyclosporine A reserpine blocked calcein-AM transport drugs minimal effect, respectively, blocking calcein-AM. In contrast, ditekiren, linear hexapeptide, readily preferentially inhibited three structural analogs ditekiren one analog calcein-AM, not as potently ditekiren. These are first reveal has distinct properties