Comparison of drug permeabilities across the blood-retinal barrier, blood-aqueous humor barrier, and blood-brain barrier.

Drugs vary in their ability to permeate the blood-retinal barrier (BRB), blood-aqueous humor barrier (BAB), and blood-brain barrier (BBB) and the factors affecting the drug permeation remain unclear. In this study, the permeability of various substances across BRB, BAB, and BBB in rats was determined using the brain uptake index (BUI), retinal uptake index (RUI), and aqueous humor uptake index (AHUI) methods. Lipophilic substances showed high permeabilities across BBB and BRB.

Involvement of choline transporter-like proteins, CTL1 and CTL2, in glucocorticoid-induced acceleration of phosphatidylcholine synthesis via increased choline uptake.

Phosphatidylcholine (PC) production is accelerated by glucocorticoid, such as dexamethasone (DEX), which enhances fetal lung maturation, promotes differentiation of alveolar type II (ATII) cells, and increases production of both lipid and protein components of lung surfactant. We previously demonstrated that inhibition of choline uptake by ATII cells leads to a decrease of PC synthesis. Since choline uptake may play a critical role in PC production and lung surfactant homeostasis for normal breathing, it is of interest to characterize transporters controlling the disposition of choline in ATII cells.

Effect of glucocorticoid receptor ligand dexamethasone on the expression of organic cation transporter in rat liver.

Since rat organic cation transporter 1 (Oct1, Slc22a1) is expressed mainly in the liver and mediates drug transport, its activity may determine the hepatic handling of cationic drugs. Here, we studied the regulation mechanism of the expression of rat Oct1, focusing on the nuclear receptors. Various nuclear receptors are considered to regulate expressions of many genes for membrane transporters and enzymes that are involved in the drug absorption and disposition.

Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells.

Purpose: We investigated whether gefitinib, an anticancer agent, inhibits phosphatidylcholine (PC) biosynthesis and choline uptake by alveolar epithelial type II cells.

Materials And Methods: Uptake of choline and PC biosynthesis were examined in vitro, using human alveolar epithelia-derived cell line A549 and rat alveolar type (AT) II cells as models.

Results: Gefitinib reduced the incorporation of [3H]choline into PC in A549 and rat ATII cells.

Effect of pregnane X receptor ligand on pharmacokinetics of substrates of organic cation transporter Oct1 in rats.

Because rat organic cation transporter 1 (Oct1, SLC22a1) is expressed mainly in the liver and mediates drug transport, its activity may determine the hepatic handling of cationic drugs. Here, we studied the regulation mechanism of the expression of Oct1, focusing on the nuclear receptors. In vitro studies using cultured hepatocytes indicated that expression of Oct1 was up-regulated by treatment with pregnenolone-16 alpha-carbonitrile (PCN) and by overexpression of rat pregnane X receptor (PXR).