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 H₁antagonist 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 µl/mg protein/min) and the transcellular permeability coefficient (488 µl/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.