|
Journal of Lipid Research, Vol. 41, 1841-1848, November 2000
Copyright © 2000 by Lipid Research, Inc.
Functional expression of a high affinity mammalian hepatic choline/organic cation transporter
Christian J. Sinclairb,
Kenneth D. Chib,
Veedamali Subramanianb,
Kristine L. Warda,b,c, and
Richard M. Greena,b,c
a Division of Gastroenterology and Hepatology, Northwestern University Medical School, Chicago, IL 60611
b Section of Digestive and Liver Diseases, University of Illinois at Chicago College of Medicine, Chicago, IL 60612
c Chicago Veterans Administration Medical Center, Chicago, IL 60611
Correspondence to:
Richard M. Green
Uptake by the liver of the organic cation and essential nutrient choline is required for the hepatic synthesis of phosphatidylcholine. Uptake of other organic cations is also important for the metabolism and secretion of numerous endobiotics and drugs. Although a high affinity mammalian hepatic choline transporter has been kinetically defined, it has not been previously identified. We have developed stable transfectants of BALB/3T3 cells, using a murine member of the organic cation transporter gene family (mOct1/Slc22a1), and used these cells to characterize the transport of the organic cation choline and model organic cation tetraethylammonium (TEA). Functional expression of mOct1/Slc22a1 in BALB/3T3 cells confers the saturable, temperature-dependent uptake of choline with a Km of 42 µM, and uptake of TEA with a Km of 43 µM. We subsequently used our cell culture uptake system to kinetically define in HepG2 cells a high affinity choline uptake process, which transports choline with a Km similar to that of mOct1/Slc22a1 protein. We also demonstrated that organic cation transport by mOct1/Slc22a1 is inhibited by several organic cations, and that the gene is expressed in the perinatal period, at a time when phosphatidylcholine synthesis increases.
We conclude that mOct1/Slc22a1 encodes a high affinity mammalian hepatic choline/organic cation transporter. This transporter may be important for hepatic phosphatidylcholine synthesis, and for the metabolism and secretion of many organic cationic drugs. Sinclair, C. J., K. D. Chi, V. Subramanian, K. L. Ward, and R. M. Green. Functional expression of a high affinity mammalian hepatic choline/organic cation transporter. J. Lipid Res. 2000. 41: 1841;1848.
Supplementary key words:
choline, liver, phospholipid

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
V. Michel, Z. Yuan, S. Ramsubir, and M. Bakovic
Choline Transport for Phospholipid Synthesis
Exp Biol Med,
May 1, 2006;
231(5):
490 - 504.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Nie, S. Sweetser, M. Rinella, and R. M. Green
Transcriptional regulation of murine Slc22a1 (Oct1) by peroxisome proliferator agonist receptor-{alpha} and -{gamma}
Am J Physiol Gastrointest Liver Physiol,
February 1, 2005;
288(2):
G207 - G212.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. L. Miakotina, M. Agassandian, L. Shi, D. C. Look, and R. K. Mallampalli
Adenovirus stimulates choline efflux by increasing expression of organic cation transporter-2
Am J Physiol Lung Cell Mol Physiol,
January 1, 2005;
288(1):
L93 - L102.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. W. Jonker, E. Wagenaar, C. A. A. M. Mol, M. Buitelaar, H. Koepsell, J. W. Smit, and A. H. Schinkel
Reduced Hepatic Uptake and Intestinal Excretion of Organic Cations in Mice with a Targeted Disruption of the Organic Cation Transporter 1 (Oct1 [Slc22a1]) Gene
Mol. Cell. Biol.,
August 15, 2001;
21(16):
5471 - 5477.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|