Riboflavin Homeostasis in the Central Nervous System

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Abstract
The mechanisms by which riboflavine, which is not synthesized in mammals, enters and leaves brain, CSF and choroid plexus were investigated by injecting [14C]riboflavine i.v. or intraventricularly. Tracer amounts of [14C]riboflavine with or without FMN were infused i.v. at a constant rate into normal, starved or probenecid-pretreated rabbits. At 3 h, [14C]riboflavine readily entered choroid plexus and brain, and to a much lesser extent, CSF. Over 85% of the [14C]riboflavine in brain and choroid plexus was present as [14C]hMN and [14C]FAD. The addition of 0.2 mmol/kg FMN to the infusate markedly depressed the relative entry of [14C]riboflavine into brain, choroid plexus, and, in a lesser way, CSF, whereas starvation increased the relative entry of [1I4C]riboflavine into brain and choroid plexus. After intraventricular injection (2 h), most of the [14C]riboflavine was very rapidly cleared from CSF into blood. Some of the [14C]riboflavine entered brain, where over 85% of the 14C was present as [14C]FMN plus [14C]FAD. The addition of 1.23 .mu.mol FAD (which was rapidly hydrolyzed to riboflavine) to the injectate decreased the clearance of [14C]riboflavine from CSF and the phosphorylation of [14C]riboflavine in brain. Probenecid in the injectate also decreased the clearance of [14C]riboflavine from CSF. The control of entry and exit of riboflavine is the mechanism, at least in part, by which total riboflavine levels in brain cells and CSF are regulated. Penetration of riboflavine through the blood-brain barrier, saturable efflux of riboflavine from CSF and saturable entry of riboflavine into brain cells are 3 distinct parts of the homeostatic system for total riboflavine in the CNS.