The uptake of estrone-3-sulfate is mediated by Na+-independent transporter(s). Inhibitor of estrone-3-sulfate transporter suppressed the transcription and cell proliferation induced by estrone-3-sulfate in MCF-7 cells. The results provide the basis of a novel strategy for breast cancer treatment by focusing on the transporter responsible for the uptake of estrone-3-sulfate.

The present study was designed to identify the organic anion transporting polypeptide (OATP) molecule(s) responsible for the uptake of beta-lactam antibiotics in human liver, using cryopreserved hepatocytes, as well as Xenopus oocytes and cultured cells expressing human OATPs. Nafcillin uptake by human hepatocytes was saturable with a Km of 533 microM. In vitro uptake studies revealed that OATP1B3 and OATP1B1 transported nafcillin with Km values of 74 microM and 11 mM, respectively. Analysis by the relative activity factor method suggested that OATP1B3 contributes mainly to nafcillin uptake and OATP1B1 contributes moderately. This conclusion was supported by the results of a study with selective inhibitors. Furthermore, OATP1B3 transported six other beta-lactam antibiotics, and their uptake clearances by OATP1B3 correlated well with those mediated by rat Oatp1a4, which is the predominant contributor to basolateral uptake of nafcillin by rat hepatocytes. These findings suggest that OATP1B3 plays a major role in the hepatic uptake of beta-lactam antibiotics in humans, and probably corresponds functionally to Oatp1a4 in rat liver.

No abstract

These findings suggest that Oatp2 plays a key role in the hepatic uptake of nafcillin and most other beta-lactam antibiotics in rats.

Carnitine is essential for the acquisition of motility and maturation of spermatozoa in the epididymis, and is accumulated in epididymal fluid. In this study, carnitine transport into primary-cultured rat epididymal epithelial cells was characterized to clarify the nature of the transporter molecules involved. Uptake of carnitine by primary-cultured epididymal epithelial cells was time, Na 1 and concentration dependent. Kinetic analysis of carnitine uptake by the cells revealed the involvement of high-and low-affinity transport systems with Km values of 21 mM and 2.2 mM respectively. The uptake of carnitine by the cells was significantly reduced by inhibitors of carnitine/organic cation transporter (OCTN2), such as carnitine analogues and cationic compounds. In RT-PCR analysis, OCTN2 expression was detected. These results demonstrated that the high-affinity carnitine transporter OCTN2, which is localized at the basolateral membrane of epididymal epithelial cells, mediates carnitine supply into those cells from the systemic circulation as the first step of permeation from blood to spermatozoa.Reproduction (