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| Content Provider | PubMed Central |
|---|---|
| Author | Pan, Guoyu Winter, Tate N. Roberts, John C. Fairbanks, Carolyn A. Elmquist, William F. |
| Abstract | Stably transfected cell models are routinely used to examine drug-transporter interactions. In one such model of bcrp1-transfected MDCKII cells, we observed a significant enhancement of organic cation intracellular accumulation. Therefore, our goal was to further explore the expression and functional consequences of this cation transport system. Transport assays were carried out in wild-type and bcrp1-transfected MDCKII cells to examine uptake of [3H]-prazosin (bcrp1 positive control), [3H]-agmatine, [3H]-TEA, and [14C]-choline. RT-PCR was employed to determine the mRNA levels of bcrp1 and OCT2/OCT3. Western-blots were used to evaluate corresponding protein levels. Accumulation studies determined a significant increase in the uptake of the organic cations agmatine, TEA, and choline in bcrp1-transfected cells when compared to wild-type cells. Directional transport of [3H]-agmatine showed a significantly greater apical (A) to basolateral (B) than B-to-A flux in both cell types. In spite of this, the A-to-B flux was significantly lower in bcrp1-transfected cells. RT-PCR revealed 10-fold higher OCT2 mRNA levels in bcrp1-transfected cells, with no changes in OCT3. OCT2 protein expression was approximately 3.5-fold higher in bcrp1-transfected cells. The up-regulation of OCT2 in bcrp1-transfected MDCKII cells contributed to a significant enhancement in the uptake of several organic cations. These results are consistent with the endogenous expression of OCT2 in the kidney tubule, and may be related to the expression and function of bcrp1. Our findings illustrate the importance of understanding how endogenous transporters, which may compete for common substrates, may be influenced by the over-expression and enhanced function of recombinant transport systems. |
| Related Links | http://dx.doi.org/10.1021/mp900177r |
| Starting Page | 138 |
| File Format | |
| ISSN | 15438392 |
| e-ISSN | 15438392 |
| Journal | Molecular pharmaceutics |
| Issue Number | 1 |
| Volume Number | 7 |
| Language | English |
| Publisher Date | 2010-02-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Drug Discovery Molecular Medicine Pharmaceutical Science |
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