title: Carrier-mediated transport of H1-antagonist at the blood-brain barrier: mepyramine uptake into bovine brain capillary endothelial cells in primary monolayer cultures.
abstract: The transport mechanism of the H1-antagonist mepyramine at the blood-brain barrier (BBB) was studied by using primary cultured monolayers of bovine brain capillary endothelial cells (BCEC). The initial uptake of [3H]mepyramine into the BCEC showed strong temperature and concentration dependency, indicating that it involves both saturable and nonsaturable processes. Transport at the luminal membrane may be the rate-limiting process in the transcellular transport, since the values of the uptake coefficient of [3H]mepyramine at the luminal membrane (609 microliters/mg protein/min) and the transcellular permeability coefficient (488 microliters/mg protein/min) are very similar. The initial uptake of [3H]mepyramine was not affected by metabolic inhibitors, but was stimulated by preloading with the drug. Mepyramine appears to be transported into the BCEC by a carrier-mediated transport system which does not require metabolic energy, probably via a facilitated diffusion mechanism.
authors.affiliation: Research Department, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamazaki
authors.forename: T
authors.initials: T
authors.lastname: Terasaki
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
authors.forename: O
authors.initials: O
authors.lastname: Nagata
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D011738:Pyrilamine / Q000378:metabolism / Q000493:pharmacokinetics*; D014316:Tritium
chemical_list: D002352:Carrier Proteins; D014316:Tritium; D011738:Pyrilamine