title: A comparison of drug transport through cultured monolayers of bovine brain capillary and bovine aortic endothelial cells.
abstract: To examine how efficient primary cultured brain capillary endothelial cells are as an in vitro blood-brain barrier (BBB) system with regard to drug transport, we compared bovine brain capillary endothelial cells (BBCEC) with bovine aortic endothelial cells (BAEC). Paracellular and transcellular transport were examined. [14C]Sucrose and fluorescein isothiocyanate-dextran (FITC-dextran)(average molecular weight about 4400 and 71200) were used as indices of paracellular transport. The permeability coefficients of [14C]sucrose and FITC-dextran through BBCEC monolayers were about 3 and 30-40 fold lower than those through BAEC monolayers, respectively. Transcellular transport was examined by means of [3H]leucine and [3H]alanine uptake studies. The Km value (Michaelis constant) of the amino acid uptake was lower in BBCEC than in BAEC. BBCEC had higher alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) activity than BAEC when cultured in vitro. These results suggest that BBCEC are suitable for drug transport studies across the BBB in vitro.
authors.affiliation: Faculty of Pharmaceutical Science, Osaka University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Hashioka
authors.forename: N
authors.initials: N
authors.lastname: Utoguchi
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: S
authors.initials: S
authors.lastname: Nakagawa
authors.forename: T
authors.initials: T
authors.lastname: Mayumi
mesh_terms: D000409:Alanine / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001011:Aorta; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003911:Dextrans / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D008970:Molecular Weight; D010590:Phalloidine / Q000737:chemistry; D012235:Rhodamines / Q000737:chemistry; D013395:Sucrose / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D003911:Dextrans; D012235:Rhodamines; D010590:Phalloidine; D013395:Sucrose; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D007930:Leucine; D016650:Fluorescein-5-isothiocyanate; D000409:Alanine