CARRIER-MEDIATED TRANSPORT OF H-1-ANTAGONIST AT THE BLOOD-BRAIN-BARRIER - MEPYRAMINE UPTAKE INTO BOVINE BRAIN CAPILLARY ENDOTHELIAL-CELLS IN PRIMARY MONOLAYER-CULTURES

The transport mechanism of the H-1-antagonist mepyramine at the blood- brain barrier (BBB) was studied by using primary cultured monolayers o f bovine brain capillary endothelial cells (BCEC). The initial uptake of [H-3]mepyramine into the BCEC showed strong temperature and concent ration dependency, indicating that it involves both saturable and nons aturable processes. Transport at the luminal membrane may be the rate- limiting process in the transcellular transport, since the values of t he uptake coefficient of [H-3]mepyramine at the luminal membrane (609 mu l/mg protein/min) and the transcellular permeability coefficient (4 88 mu l/mg protein/min) are very similar. The initial uptake of [H-3]m epyramine was not affected by metabolic inhibitors, but was stimulated by preloading with the drug. Mepyramine appears to be transported int o the BCEC by a carrier-mediated transport system which does not requi re metabolic energy, probably via a facilitated diffusion mechanism.