ArticleThe Journal of pharmacology and experimental therapeutics2010
Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Doubly protected ester prodrug of 5-aminolevulinic acid for enhanced cell uptake and photoinactivation.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026Article
- Substrate recognition and transport mechanism of the human proton-coupled amino-acid transporter 1 (SLC36A1).Nature communications · 2026Article
- Doubly protected ester prodrug of 5-aminolevulinic acid for enhanced cell uptake and photoinactivation.Research square · 2026Article
- Exploring Amino Acid Transporters as Therapeutic Targets for Cancer: An Examination of Inhibitor Structures, Selectivity Issues, and Discovery Approaches.Pharmaceutics · 2024Review
- Review
- A Thiosemicarbazone Derivative as a Booster in Photodynamic Therapy-A Way to Improve the Therapeutic Effect.International journal of molecular sciences · 2022Article
- SNAT2 is responsible for hyperosmotic induced sarcosine and glycine uptake in human prostate PC-3 cells.Pflugers Archiv : European journal of physiology · 2022Article
- PEPT1 is essential for the growth of pancreatic cancer cells: a viable drug target.The Biochemical journal · 2021Article
- Photoactivatable metabolic warheads enable precise and safe ablation of target cells in vivo.Nature communications · 2021Article
- Key transporters leading to specific protoporphyrin IX accumulation in cancer cell following administration of aminolevulinic acid in photodynamic therapy/diagnosis.International journal of clinical oncology · 2021Review
- Recent advances in understanding prodrug transport through the SLC15 family of proton-coupled transporters.Biochemical Society transactions · 2020Review
- In order for the light to shine so brightly, the darkness must be present-why do cancers fluoresce with 5-aminolaevulinic acid?British journal of cancer · 2019Review
- Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.Comprehensive Physiology · 2018Review
- The proton-coupled oligopeptide transporter 1 plays a major role in the intestinal permeability and absorption of 5-aminolevulinic acid.British journal of pharmacology · 2016Article
- An oncologist׳s friend: How Xenopus contributes to cancer research.Developmental biology · 2015Review
- Role of solute carriers in response to anticancer drugs.Molecular and cellular therapies · 2014Review
- The human proton-coupled folate transporter: Biology and therapeutic applications to cancer.Cancer biology & therapy · 2012Review
- The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport.British journal of pharmacology · 2011Review
- SLC36A4 (hPAT4) is a high affinity amino acid transporter when expressed in Xenopus laevis oocytes.The Journal of biological chemistry · 2011Article
- Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2).Biochimica et biophysica acta · 2011Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
5-Aminolevulinic acid (ALA) is a prodrug used in photodynamic therapy, fluorescent diagnosis, and fluorescent-guided resection because it leads to accumulation of the photosensitizer protoporphyrin IX (PpIX) in tumor tissues. ALA has good oral bioavailability, but high oral doses are required to obtain selective PpIX accumulation in colonic tumors because accumulation is also observed in normal gut mucosa. Structural similarities between ALA and GABA led us to test the hypothesis that the H(+)-coupled amino acid transporter PAT1 (SLC36A1) will contribute to luminal ALA uptake. Radiolabel uptake and electrophysiological measurements identified PAT1-mediated H(+)-coupled ALA symport after heterologous expression in Xenopus oocytes. The selectivity of the nontransported inhibitors 5-hydroxytryptophan and 4-aminomethylbenzoic acid for, respectively, PAT1 and the H(+)-coupled di/tripeptide transporter PepT1 (SLC15A1) were examined. 5-Hydroxytryptophan selectively inhibited PAT1-mediated amino acid uptake across the brush-border membrane of the human intestinal (Caco-2) epithelium whereas 4-aminomethylbenzoic acid selectively inhibited PepT1-mediated dipeptide uptake. The inhibitory effects of 5-hydroxytryptophan and 4-aminomethylbenzoic acid were additive, demonstrating that both PAT1 and PepT1 contribute to intestinal transport of ALA. This is the first demonstration of overlap in substrate specificity between these distinct transporters for amino acids and dipeptides. PAT1 and PepT1 expression was monitored by reverse transcriptase-polymerase chain reaction using paired samples of normal and cancer tissue from human colon. mRNA for both transporters was detected. PepT1 mRNA was increased 2.3-fold in cancer tissues. Thus, increased PepT1 expression in colonic cancer could contribute to the increased PpIX accumulation observed. Selective inhibition of PAT1 could enhance PpIX loading in tumor tissue relative to that in normal tissue.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.