Manganese (Mn) Transport Across the Rat Blood-brain Barrier: Saturable and Transferrin-dependent Transport Mechanisms

Using a single capillary pass technique, the transport of manganese (Mn) across the rat blood-brain barrier (BBB) was characterized. Initial rate measurements (15 s) of Mn2+ [0-1000 microM] accumulation in rat brains clearly indicated saturation kinetics by both 1/v vs. 1/s plots, and plots of v vs. [s]. Common carotid injection of freshly mixed Mn2+ with transferrin at a 1:10 molar ratio did not result in a significant change in the initial rate of Mn brain levels compared with injection of Mn2+ alone. However, when Mn2+ was incubated at 25 degrees C in the presence of transferrin at a 1:10 ratio for up to 5 days prior to common carotid injection, the initial rate of Mn uptake by brain was incubation-time-dependent, increasing linearly with prolonged incubations. These findings suggest that the saturable component of divalent Mn transport into brain represents but one of the transport mechanisms for Mn across the BBB. A second transport system for Mn may occur by a transferrin-conjugated Mn transport system.