Kullak-Ublick G A, Fisch T, Oswald M, Hagenbuch B, Meier P J, Beuers U, Paumgartner G
Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
FEBS Lett. 1998 Mar 13;424(3):173-6. doi: 10.1016/s0014-5793(98)00168-9.
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.
硫酸脱氢表雄酮（DHEAS）是人体内主要的循环类固醇。在药理学上，它具有显著的神经精神效应。由于尚未确定其靶受体，我们研究了多特异性类固醇载体有机阴离子转运多肽（OATP）是否转运DHEAS。人肝OATP在非洲爪蟾卵母细胞中的表达导致了[3H]DHEAS的高亲和力、部分依赖钠离子的摄取（Km：6.6微摩尔/升）。DHEAS的转运受到溴磺酞、胆汁酸、硫酸化雌激素和地塞米松的抑制。Northern印迹分析显示OATP在人脑中广泛表达。这些数据确定OATP是DHEAS在人肝脏和大脑中的首个已知靶蛋白。
