title: Dehydroepiandrosterone sulfate (DHEAS): identification of a carrier protein in human liver and brain.
abstract: Dehydroepiandrosterone sulfate (DHEAS) is the major circulating steroid in man. Pharmacologically, it exerts marked neuropsychiatric effects. Since no target receptor has been identified, we investigated whether the organic anion transporting polypeptide (OATP), a multispecific steroid carrier, transports DHEAS. Expression of the human liver OATP in Xenopus laevis oocytes resulted in high-affinity, partially Na+-dependent uptake of [3H]DHEAS (Km: 6.6 micromol/l). DHEAS transport was inhibited by bromosulfophthalein, bile acids, sulfated estrogens and dexamethasone. Northern blot analysis showed widespread expression of OATP in human brain. These data identify OATP as the first known target protein of DHEAS in human liver and brain.
authors.affiliation: Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany. kullak@med2.med.uni-muenchen.de
authors.forename: G A
authors.initials: GA
authors.lastname: Kullak-Ublick
authors.forename: T
authors.initials: T
authors.lastname: Fisch
authors.forename: M
authors.initials: M
authors.lastname: Oswald
authors.forename: B
authors.initials: B
authors.lastname: Hagenbuch
authors.forename: P J
authors.initials: PJ
authors.lastname: Meier
authors.forename: U
authors.initials: U
authors.lastname: Beuers
authors.forename: G
authors.initials: G
authors.lastname: Paumgartner
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014316:Tritium; D014982:Xenopus laevis
chemical_list: D027321:Anion Transport Proteins; D002352:Carrier Proteins; D011994:Recombinant Proteins; D014316:Tritium; D019314:Dehydroepiandrosterone Sulfate