10854277

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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 alpha-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.

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MEDLINE

0022-3042

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321-8

pubmed-meshheading:10854277-Aminolevulinic Acid, pubmed-meshheading:10854277-Animals, pubmed-meshheading:10854277-Bicarbonates, pubmed-meshheading:10854277-Biological Transport, pubmed-meshheading:10854277-Blood-Brain Barrier, pubmed-meshheading:10854277-Blotting, Western, pubmed-meshheading:10854277-Buffers, pubmed-meshheading:10854277-Captopril, pubmed-meshheading:10854277-Carrier Proteins, pubmed-meshheading:10854277-Cerebrospinal Fluid, pubmed-meshheading:10854277-Choroid Plexus, pubmed-meshheading:10854277-Hydrogen-Ion Concentration, pubmed-meshheading:10854277-Male, pubmed-meshheading:10854277-Rats, pubmed-meshheading:10854277-Rats, Sprague-Dawley, pubmed-meshheading:10854277-Sodium, pubmed-meshheading:10854277-Sodium-Bicarbonate Symporters, pubmed-meshheading:10854277-Symporters, pubmed-meshheading:10854277-Tritium

Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus.

Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.