Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2
Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2
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DOI：
10.1074/jbc.273.35.22395
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发表时间：
1998-08-28
影响因子：
4.8
通讯作者：
Yawo, H
中科院分区：
文献类型：
--
作者：
Abe, T;Kakyo, M;Yawo, H
从大鼠视网膜cDNA文库中分离到两个有机阴离子转运子亚型Oatp2和Oatp3的互补DNA，它们负责运输甲状腺激素和牛磺胆酸。Oatp2的序列与最近报道的(Noe，B，Hagenbuch，B，Stieger，B，和Meier，P，J，(1997)Proc)相同。Natl，Acad，Sci，U.S.A.94,10346-10350)，而Oatp3的序列是新的。OATP3由670个氨基酸残基组成，具有有机阴离子转运蛋白家族共同的结构，具有12个假定的跨膜片段。注射Oatp2和Oatp3CRNAs的卵母细胞可饱和摄取牛磺胆酸。Oatp2和Oatp3CRNA注射的卵母细胞对甲状腺激素和三碘甲腺原氨酸也有明显的摄取。Northern印迹和原位分析表明，Oatp2基因在中枢神经系统的神经细胞中广泛表达，特别是在海马区、小脑、脉络丛以及视网膜和肝脏中。Oatp3基因在肾脏中高表达，在视网膜中高表达。这表明Oatp2和Oatp3是参与甲状腺激素在脑、视网膜、肝脏和肾脏运输的多功能转运体。
Two complementary DNAs for the organic anion transporter subtypes oatp2 and oatp3, which transport thyroid hormones as well as taurocholate, were isolated from a rat retina cDNA library. The sequence of oatp2 is identical to that recently reported (Noe, B,, Hagenbuch, B,, Stieger, B,, and Meier, P, J, (1997) Proc. Natl, Acad, Sci, U.S.A. 94, 10346-10350), whereas the sequence of oatp3 is novel. oatp3 consists of 670 amino acid residues and exhibits a structural architecture common to the organic anion transporter family, possessing the 12 putative membrane-spanning segments. Oocytes injected with oatp2 and oatp3 cRNAs showed taurocholate uptake in a saturable manner. The oatp2 and oatp3 cRNA-injected oocytes also showed significant uptake of both thyroxine and triiodothyronine. Northern blot and in situ analyses showed that the oatp2 mRNA was widely expressed in neuronal cells of the central nervous system, especially in the hippocampus, cerebellum, and choroid plexus as well as in the retina and liver. The oatp3 mRNA was highly expressed in the kidney and moderately abundant in the retina. This suggests that oatp2 and oatp3 are multifunctional transporters involved in the transport of thyroid hormones in the brain, retina, liver, and kidney.