Dr. Tadatoshi Tanino
Dr. Yukari Ueda
Microvascular endothelial cells forms a physical barrier that separates blood from tissue. Communication between blood and tissue occurs through the delivery of drug molecules and circulating substances across the endothelial barrier. Research of our group is focused on the regulation of the pharmacokinetic barrier function in cultured brain and lung microvascular endothelial cells.
1) a permeable barrier:
Expression of tight junction proteins such as claudin, occludin and zonula occludens.
Paracellular permeability clearance.
Down regulation of tight junction protein expression and open of inter-endothelial-cell
2) a metabolic barrier:
Activities of drug-metabolizing enzymes (CYPs and FMOs) in cultured brain and lung microvascular endothelial cells.
Expression of CYPs and FMOs proteins.
Enzyme induction and detoxification system in endothelial cells.
3) Alteration in a pharmacokinetic barrier function in brain and lung microvascular endothelial cells in pathological processes such as diabetes, inflammation and stress.
Although the presence of tight junction between the endothelial cells limit the distribution into the central nervous system (CNS), our research expect approaches to enhance drug delivery to CNS. On the other hand, we may be able to construct efficient metabolic barrier system to prevent the entry of exogenous origin such as nicotine inhaled in tobacco smoke or air-pollution substances to the circulating system in lung endothelial cells, besides hepatic metabolism.