The relationship of riboflavin transport to the transport of other substances including drugs in rabbit choroid plexus, the anatomical locus of the blood-cerebrospinal fluid barrier, and brain cells were studied in vivo and in vitro. In vitro, the ability of rabbit choroid plexus to transport riboflavin from the medium (cerebrospinal fluid surface) through the choroid plexus epithelial cells into the extracellular and vascular spaces of the choroid plexus was documented using fluorescence microscopy. These studies provided further evidence that riboflavin is transported from cerebrospinal fluid to blood via the choroid plexus. The transport of [14C]riboflavin by the isolated choroid plexus was inhibited by thiol agents, ouabain, theophylline, various flavins (lumiflavin and lumichrome > sugar containing flavins), and cyclic organic acids including penicillin and fluorescein. Riboflavin inhibited [14C]penicillin transport competitively and the inhibition constant (K1) for riboflavin equaled the concentration of riboflavin at which the saturable transport system for riboflavin is 50% saturated (KT). These and other data suggest that riboflavin, penicillin, and possibly fluorescein are transported by the same transport system in choroid plexus. In vivo, the intra-ventricular injection or riboflavin and [14C]penicillin inhibited [14C]penicillin transport from cerebrospinal fluid. In vitro, various flavins (riboflavin > other sugar-containing flavins > lumiflavin > lumichrome) inhibited [14C]riboflavin accumulation by brain slices. These studies support the notions that: (a) riboflavin accumulation by choroid plexus (active transport) is quite different from that in brain cells (facilitated diffusion and intracellular trapping), and (b) therapeutically important cyclic organic acids (e.g., penicillin) are transported fom cerebrospinal fluid by the riboflavin transport system in choroid plexus.
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