Document Detail

Delta-aminolevulinic acid is a substrate for the amino acid transporter SLC36A1 (hPAT1).
MedLine Citation:
PMID:  20128809     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: delta-Aminolevulinic acid (ALA) is used in cancer patients for photodynamic diagnosis or therapy. Oral administration of ALA has been used in patients with prostate and bladder cancer. The present aim was to investigate the mechanism of intestinal absorption of ALA and its transport via the amino acid transporter SLC36A1.
EXPERIMENTAL APPROACH: In vitro investigations of ALA affinity for and uptake via SLC36A1 and SLC15A1 were performed in Caco-2 cell monolayers. Interaction of ALA with SLC15A1 was investigated in MDCK/SLC15A1 cells, whereas interactions with SLC36A1 were investigated in COS-7 cells transiently expressing SLC36A1.
KEY RESULTS: ALA inhibited SLC36A1-mediated L-[(3)H]Pro and SLC15A1-mediated [(14)C]Gly-Sar uptake in Caco-2 cell monolayers with IC(50) values of 11.3 and 2.1 mM respectively. In SLC36A1-expressing COS-7 cells, the uptake of [(14)C]ALA was saturable with a K(m) value of 6.8 +/- 3.0 mM and a V(max) of 96 +/- 13 pmol x cm(-2) x min(-1). Uptake of [(14)C]ALA was pH and concentration dependent, and could be inhibited by glycine, proline and GABA. In a membrane potential assay, translocation of ALA via SLC36A1 was concentration dependent, with a K(m) value of 3.8 +/- 1.0 mM. ALA is thus a substrate for SLC36A1. In Caco-2 cells, apical [(14)C]ALA uptake was pH dependent, but Na(+) independent, and completely inhibited by 5-hydroxy-L-tryptophan and L-4,4'-biphenylalanyl-l-proline. CONCLUSIONS AND IMPLICATIONS. ALA was a substrate for SLC36A1, and the apical absorption in Caco-2 cell was only mediated by SLC36A1 and SLC15A1. This advances our understanding of intestinal absorption mechanisms of ALA, as well as its potential for drug interactions.
S Frølund; O C Marquez; M Larsen; B Brodin; C U Nielsen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-27
Journal Detail:
Title:  British journal of pharmacology     Volume:  159     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-07-12     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1339-53     Citation Subset:  IM    
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
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MeSH Terms
Amino Acid Transport Systems / metabolism*
Aminolevulinic Acid / pharmacokinetics,  pharmacology*
Biological Transport
COS Cells
Caco-2 Cells
Cercopithecus aethiops
Dose-Response Relationship, Drug
Intestinal Absorption
Intestines / metabolism*
Membrane Potentials / drug effects
Oligopeptides / pharmacokinetics,  pharmacology
Photosensitizing Agents / pharmacokinetics,  pharmacology*
Substrate Specificity
Symporters / metabolism*
Reg. No./Substance:
0/Amino Acid Transport Systems; 0/Oligopeptides; 0/Photosensitizing Agents; 0/SLC15A1 protein, human; 0/SLC36A1 protein, human; 0/Symporters; 106-60-5/Aminolevulinic Acid

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