Carrier-mediated transport of H1-antagonist at the blood-brain barrier: mepyramine uptake into bovine brain capillary endothelial cells in primary monolayer cultures.
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.
Yamazaki
M
M
Research Department, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
Terasaki
T
T
Yoshioka
K
K
Nagata
O
O
Kato
H
H
Ito
Y
Y
Tsuji
A
A
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
D002352:Carrier Proteins; D014316:Tritium; D011738:Pyrilamine