251. Dehydroepiandrosterone sulfate (DHEAS): identification of a carrier protein in human liver and brain.
- Author
-
Kullak-Ublick GA, Fisch T, Oswald M, Hagenbuch B, Meier PJ, Beuers U, and Paumgartner G
- Subjects
- Animals, Anion Transport Proteins, Blotting, Northern, Carrier Proteins drug effects, Carrier Proteins genetics, Dehydroepiandrosterone Sulfate pharmacokinetics, Female, Humans, Liver chemistry, Liver metabolism, Oocytes physiology, Recombinant Proteins genetics, Recombinant Proteins metabolism, Tritium, Xenopus laevis, Brain metabolism, Carrier Proteins metabolism, Dehydroepiandrosterone Sulfate metabolism
- 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.
- Published
- 1998
- Full Text
- View/download PDF