A COMPARISON OF DRUG TRANSPORT THROUGH CULTURED MONOLAYERS OF BOVINE BRAIN CAPILLARY AND BOVINE AORTIC ENDOTHELIAL-CELLS

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. [C-14]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 [C-14]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 [H-3]leucine and [H-3]alanine uptake studies. The K-m 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.