Abstract：
:Understanding the mechanisms of transport processes in the placenta can improve the safety and efficacy of drug delivery during pregnancy. Functional studies of organic cation transporters (OCTs) are usually carried out using radioactivity, and a fluorescent marker would add flexibility to experimental methods. As a published substrate for OCT1 and OCT2, the fluorescent compound 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (4-Di-1-ASP) was chosen as a candidate for studying placental OCT function in BeWo cells. The expression of OCT1 and OCT2 was also investigated in BeWo cells, an established human choriocarcinoma trophoblastic cell line frequently used as an in vitro model of the rate-limiting barrier for maternal-fetal exchange of drugs and nutrients within the placenta. 4-Di-1-ASP was taken up into BeWo cells by a low-affinity, carrier-mediated process exhibiting a Km of 580+/-110 microM and Vmax of 97+/-9 nmol/mg protein/30 min, and asymmetric transport was observed, with greater permeability in the apical to basolateral (maternal-to-fetal) direction. However, RT-PCR revealed no expression of OCT1 or OCT2 in either BeWo cells or primary cultured human cytotrophoblast cells, and OCT substrates such as TEA and choline did not inhibit the uptake of 4-Di-1-ASP. Although the uptake of this fluorescent compound in BeWo cells is not mediated by an OCT, the colocalization experiments with fluorescence microscopy and inhibition studies confirmed significant mitochondrial uptake of 4-Di-1-ASP. Transport of 4-Di-1-ASP into the nuclear region of BeWo cells was also observed, which is likely mediated by a nucleoside transporter.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Rytting E,Bryan J,Southard M,Audus KLdoi
10.1016/j.bcp.2006.11.020subject
Has Abstractpub_date
2007-03-15 00:00:00pages
891-900issue
6eissn
0006-2952issn
1873-2968pii
S0006-2952(06)00783-0journal_volume
73pub_type
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：1997-06-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00356-1
更新日期：2000-03-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90356-n
更新日期：1992-12-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：1993-08-03 00:00:00
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journal_title：Biochemical pharmacology
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更新日期：2004-06-01 00:00:00
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更新日期：2006-04-28 00:00:00
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更新日期：2003-05-15 00:00:00
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