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Mechanisms of 5‐Aminolevulinic Acid Uptake at the Choroid Plexus
Author(s) -
Novotny A.,
Xiang J.,
Stummer W.,
Teuscher N. S.,
Smith D. E.,
Keep R. F.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750321.x
Subject(s) - choroid plexus , transporter , organic cation transport proteins , blood–brain barrier , chemistry , biochemistry , symporter , organic anion transporter 1 , solute carrier family , intracellular , organic anion , pharmacology , biology , microbiology and biotechnology , endocrinology , central nervous system , ion , organic chemistry , gene
: 5‐Aminolevulinic acid (5‐ALA) is a precursor of porphyrins and heme that has been implicated in the neuropsychiatric symptoms associated with porphyrias. It is also being used clinically to delineate malignant gliomas. The blood‐CSF barrier may be an important interface for 5‐ALA transport between blood and brain as in vivo studies have indicated 5‐ALA is taken up by the choroid plexuses whereas the normal blood‐brain barrier appears to be relatively impermeable. This study examines the mechanisms of 5‐[ 3 H]ALA uptake into isolated rat lateral ventricle choroid plexuses. Results suggest that there are two uptake mechanisms. The first was a Na + ‐independent uptake system that was pH dependent (being stimulated at low pH). Uptake was inhibited by the dipeptide Gly‐Gly and by cefadroxil, an α‐amino‐containing cephalosporin. These properties are the same as the proton‐dependent peptide transporters PEPT1 and PEPT2, which have recently been shown to transport 5‐ALA in frog oocyte expression experiments. Choroid plexus uptake was not inhibited by captopril, a PEPT1 inhibitor, suggesting PEPT2‐mediated uptake. The presence of PEPT2 and absence of PEPT1 in the choroid plexus were confirmed by western blotting. The second potential mechanism was both Na + and HCO 3 ‐ dependent and appears to be an organic anion transporter, although it is possible that removal of Na + and HCO 3 ‐ may indirectly affect PEPT2 by affecting intracellular pH. The presence of PEPT2 and a putative Na + /HCO 3 ‐ ‐dependent organic anion transporter is important not only for an understanding of 5‐ALA movement between blood and brain but also because these transporters may affect the distribution of a number of drugs between blood and CSF.