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Titolo:
Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus
Autore:
Novotny, A; Xiang, J; Stummer, W; Teuscher, NS; Smith, DE; Keep, RF;
Indirizzi:
Univ Michigan, Dept Surg Neurosurg, Ann Arbor, MI 48109 USA Univ MichiganAnn Arbor MI USA 48109 g Neurosurg, Ann Arbor, MI 48109 USA Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 Coll Pharm, Ann Arbor, MI 48109 USA Univ Michigan, Upjohn Ctr Clin Pharmacol, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 n Pharmacol, Ann Arbor, MI 48109 USA Univ Munich, Klinikum Grosshadern, Dept Neurosurg, D-8000 Munich, Germany Univ Munich Munich Germany D-8000 Dept Neurosurg, D-8000 Munich, Germany
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 1, volume: 75, anno: 2000,
pagine: 321 - 328
SICI:
0022-3042(200007)75:1<321:MO5AUA>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
DELTA-AMINOLEVULINIC-ACID; COUPLED OLIGOPEPTIDE TRANSPORTER; BLOOD-BRAIN-BARRIER; EXPRESSION CLONING; PEPTIDE TRANSPORTER; IN-VITRO; FUNCTIONAL EXPRESSION; CEREBROSPINAL-FLUID; MESSENGER-RNA; RAT-BRAIN;
Keywords:
transporters; PEPT2; organic anions; peptides; porphyrins;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Keep, RF Univ Michigan, Dept Surg Neurosurg, R5550 Kresge 1, Ann Arbor, MI48109 USA Univ Michigan R5550 Kresge 1 Ann Arbor MI USA 48109 MI 48109 USA
Citazione:
A. Novotny et al., "Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus", J NEUROCHEM, 75(1), 2000, pp. 321-328

Abstract

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 brood-brain barrier appears to be relatively impermeable, This study examines the mechanisms of 5-[H-3]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 HCO3- dependent and appears to be an organic anion transporter, although it is possible that removal of Na+ and HCO3- may indirectly affect PEPT2 by affecting intracellular pH. The presence of PEPT2 and a putative Na+/HCO3--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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/04/20 alle ore 02:33:04