alexa Blood-brain barrier transport of reduced folic acid.
Molecular Biology

Molecular Biology

Journal of Cytology & Histology

Author(s): Wu D, Pardridge WM

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Abstract PURPOSE: The brain is relatively resistant to folic acid deficiency, indicating specialized transport systems may exist for this vitamin localized within the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo. The present studies quantify the BBB transport of [3H]-methyltetrahydrofolic acid (MTFA) in vivo and in isolated human brain capillaries in vitro. METHODS: BBB transport of [3H]-MTFA was compared to that of 14C]-sucrose, a plasma volume marker, following either intravenous injection or intracarotid perfusion in anesthetized rats. Competition by 10 microM MTFA or 10 microM folic acid was examined to determine whether folic acid is also transported by the MTFA uptake system. RESULTS: The BBB permeability-surface area (PS) product of [3H]-MTFA, 1.1 +/- 0.3 microL/min/g, was 6-fold greater than that of [14C]-sucrose following intravenous injection. The BBB PS product determined by intracarotid arterial perfusion was not significantly different from the BBB PS product calculated following intravenous injection. A time- and temperature- dependent uptake of [3H]-MTFA in human brain capillaries was observed. The uptake of [3H]-MTFA by either rat brain in vivo or by human brain capillaries in vitro was equally inhibited by 10 microM concentrations of either unlabeled MTFA or unlabeled folic acid. CONCLUSIONS: (1) A saturable transport system exists at the BBB for folic acid derivatives and since this transport is equally inhibited by either folic acid or MTFA, it is inferred that this transport system is the folic acid receptor, and not the reduced folic acid carrier. (2) The presence of a folate transport system at the BBB may offer an endogenous transport system for brain drug delivery of conjugates of folates and drugs that do not normally cross the BBB in vivo.
This article was published in Pharm Res and referenced in Journal of Cytology & Histology

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