Pharmaceutics (Sakurai Lab.)

Staff
Prof. Dr. Eiichi Sakurai
Ms. Yukari Ueda

Research project
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
tight junctions.
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.

Publications

  1. Ueda Y., Yaginuma T., Sakurai Eiko, Sakurai E. N-Demethylation and N-oxidation ofimipramine in rat thoracic aortic endothelial cells. In Vitro Cell. Dev. Biol. Anim. 50 (2014) in press.
  2. Sakurai E., Ueda Y., Mori Y., Shinmyouzu Y., Sakurai Eiko. Flavin-containingmonooxygenase (FMO) protein expression and its activity in rat brain microvascular endothelial cells. Pharmacol. Pharm. 4:1-6 (2013).
  3. Ueda Y., Taira Z. Effect of anions or foods on absolute bioavailability of calcium from calcium salts in mice by pharmacokinetics. J. Exp. Pharmacol. 5: 1-7 (2013).
  4. Ueda Y., Taira Z. Pharmacokinetic characterization of calcium from three calcium salts (Calcium chloride, Calcium acetate and calcium ascorbate) in Mice. J. Hard Tissue Biol. 21: 291-298 (2012).
  5. Ueda Y., Kanayama M., Yamauchi N., Iio C., Taira Z. Effects of Hachimi-jio-ganextract on intestinal absorption of calcium in ovariectomized mice and stimulation of RANKL-induced osteoclast differentiation of Raw264.7 cells by lipopolysaccharide. J. Hard Tissue Biol. 21: 469-476 (2012).
  6. Sakurai E, Sakurai E, Ueda Y, Yagi Y; Enhancing  effect of zinc on L-histidine transport in rat lung microvascular endothelial cells. Biol Trace Elem Res., 142, 713-722 (2011).
  7. Iizuka Y, Ueda Y, Yagi Y, Sakurai E; Significant improvement of insulin resistance of GK rats by treatment with sodium selenate. Biol Trace Elem Res., 138, 265-271 (2010).
  8. Sakurai E, Sakurai H E, Watanabe T, Yanai K; Uptake of L-histidine and histamine biosynthesis at the blood-brain barrier. Inflamm Res. 58, 34-35 (2009).
  9. Ochiai Y, Itoh K, Sakurai E, Adachi M, Tanaka Y; Substrate selectivity of monoamine oxidase A, monoamine oxidase B, diamine oxidase, and semicarbazide-sensitive amine oxidase in COS-1 expression systems.  Biol Pharm Bull. 29, 2362-2366 (2006).
  10. Sakurai E, Sakurai E, Oreland L, Nishiyama S, Kato M, Watanabe T, Yanai K; Evidence for the presence of histamine uptake into the synaptosomes of rat brain.  Pharmacology, 78, 72-80 (2006).