Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner.
We have recently identified that rat organic anion transporters, polypeptide2 (oatp2) and oatp3, both of which transport thyroid hormones. However, in humans the molecular organization of the organic anion transporters has diverged, and the responsible molecule for thyroid hormone transport has not been clarified, except for human liver-specific transporter (LST-1) identified by us. In this study we isolated and characterized a novel human organic anion transporter, OATP-E from human brain. The isolated complementary DNA encodes a polypeptide of 722 amino acids with 12 transmembrane domains. A rat counterpart, oatp-E, was also identified. Homology analysis and the phylogenetic tree analysis revealed that OATP-E/oatp-E is a subfamily of the organic anion transporter. Human OATP-E transported 3,3',5-triiodo-L-thyronine (K(m), 0.9 microM), thyronine, and rT(3) in a Na(+)-independent manner. Although the clone was isolated from the brain, OATP-E messenger RNA was abundantly expressed in various peripheral tissues. The rat counterpart, oatp-E, also transported 3,3',5-triiodo-L-thyronine. In addition, in this study we revealed that human OATP, which is exclusively expressed in the brain, transported 3,3',5-triiodo-L-thyronine (K(m), 6.5 microM), T(4) (K(m), 8.0 microM), and rT(3). These data suggest that in humans, several different molecules are involved in transporting thyroid hormone: OATP in the brain, LST-1 in the liver, and OATP-E in peripheral tissues.
Fujiwara
K
K
Department of Neurophysiology, First Department of Surgery, Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai 980-8575, Japan.
Adachi
H
H
Nishio
T
T
Unno
M
M
Tokui
T
T
Okabe
M
M
Onogawa
T
T
Suzuki
T
T
Asano
N
N
Tanemoto
M
M
Seki
M
M
Shiiba
K
K
Suzuki
M
M
Kondo
Y
Y
Nunoki
K
K
Shimosegawa
T
T
Iinuma
K
K
Ito
S
S
Matsuno
S
S
Abe
T
T
D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013963:Thyroid Hormones / Q000378:metabolism*
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D013963:Thyroid Hormones