Bibliographic Details
| Title: |
Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. |
| Authors: |
Tsuyoshi Mikkatchi, David J., Takehiro Suzuki, David J., Tohru Onogawa, David J., Masayuki Tanemoto, David J., Hiroya Mizutamari, David J., Masahiro Okada, Tatsuji Chaki, David J., Masuda, Satohiro, Taro Tokui, Satohiro, Nobuaki Eto, Satohiro, Abe, Michiaki, Fumitoshi Satoh, Michiaki, Michiaki Unno, Michiaki, Takanori Hishinuma, Michiaki, Ken-ichi Inui, Sadayoshi Ito, Junichi Goto, Takaaki Abe, Michiaki |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America; 3/9/2004, Vol. 101 Issue 10, p3569-3574, 6p |
| Subject Terms: |
DIGOXIN, CARDIAC glycosides, KIDNEYS, RATS, HEART failure, BIOLOGICAL membranes |
| Abstract: |
Digoxin, which is one of the most commonly prescribed drugs for the treatment of heart failure, is mainly eliminated from the circulation by the kidney. P-glycoprotein is well characterized as a digoxin pump at the apical membrane of the nephron. However, little is known about the transport mechanism at the basolateral membrane. We have isolated an organic anion transporter (OATP4C1) from human kidney. Human OATP4C1 is the first member of the organic anion transporting polypeptide (OATP) family expressed in human kidney. The isolated cDNA encodes a polypeptide of 724 aa with 12 transmembrane domains. The genomic organization consists of 13 exons located on chromosome 5q21. Its rat counterpart, Oat4c1, is also isolated from rat kidney. Human OATP4C1 transports cardiac glycosides (digoxin, Km = 7.8 μM and ouabain, Km = 0.38 μM), thyroid hormone (triiodothyronine, Km = 5.9 μM and thyroxine), cAMP, and mehotrexate in a sodium-independent manner. Rat Oatp4c1 also transports digoxin (Km = 8.0 μM) and triiodothyronine (Km = 1.9 μM). Immunohistochemical analysis reveals that rat Oatp4c1 protein is localized at the basolateral membrane of the proximal tubule cell in the kidney. These data suggest that human OATP4C1/rat Oatp4c1 might be a first step of the transport pathway of digoxin and various compounds into urine in the kidney. [ABSTRACT FROM AUTHOR] |
|
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
