Functional expression of a high affinity mammalian hepatic choline/organic cation transporter.

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Sinclair CJ, Chi KD, Subramanian V, Ward KL, Green RM

Functional expression of a high affinity mammalian hepatic choline/organic cation transporter.

J Lipid Res. 2000 Nov;41(11):1841-8.

PubMed ID

11060354 [ View in PubMed

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Abstract

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 K(m) of 42 micrometer, and uptake of TEA with a K(m) of 43 micrometer. 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 K(m) 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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Choline	Solute carrier family 22 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Choline salicylate	Solute carrier family 22 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Quinidine	Solute carrier family 22 member 1	Protein	Humans	Unknown	Inhibitor	Details
Thiamine	Solute carrier family 22 member 1	Protein	Humans	Unknown	Substrate	Details