ArticlePharmaceutical research2004
Role of PEPT2 in the choroid plexus uptake of glycylsarcosine and 5-aminolevulinic acid: studies in wild-type and null mice.
Article in Pharmaceutical research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 40 citations in OpenAlex.
- Functional and Physiological Implications of Oligopeptide Transporters: Potential Targets for Pharmacological Interventions.The Journal of membrane biology · 2025Review
- Proton-Coupled Oligopeptide Transport (Slc15) in the Brain: Past and Future Research.Pharmaceutical research · 2023Review
- Pathogenesis of acute encephalopathy in acute hepatic porphyria.Journal of neurology · 2023Article
- Biology of Peptide Transporter 2 in Mammals: New Insights into Its Function, Structure and Regulation.Cells · 2022Review
- Choroid plexus and the blood-cerebrospinal fluid barrier in disease.Fluids and barriers of the CNS · 2020Review
- Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.Comprehensive Physiology · 2018Review
- Radiochemical Synthesis and Evaluation ofACS medicinal chemistry letters · 2017Article
- Species Differences in Human and Rodent PEPT2-Mediated Transport of Glycylsarcosine and Cefadroxil in Pichia Pastoris Transformants.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Human oligopeptide transporter 2 (PEPT2) mediates cellular uptake of polymyxins.The Journal of antimicrobial chemotherapy · 2016Article
- Choroid plexus transport: gene deletion studies.Fluids and barriers of the CNS · 2011Article
- Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences.Fluids and barriers of the CNS · 2011Article
- Xenobiotic, bile acid, and cholesterol transporters: function and regulation.Pharmacological reviews · 2010Review
- Role and relevance of PEPT2 in drug disposition, dynamics, and toxicity.Drug metabolism and pharmacokinetics · 2008Review
- PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes.Brain research · 2006Article
- Glycyl-L-glutamine disposition in rat choroid plexus epithelial cells in primary culture: role of PEPT2.Pharmaceutical research · 2005Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo determine the importance of PEPT2 in the uptake of glycylsarcosine (GlySar) and 5-aminolevulinic acid (5-ALA) in mouse choroid plexus whole tissue.
methodsUptake studies were performed in bicarbonate artificial cerebrospinal fluid buffer using choroid plexuses isolated from PEPT2+/+ and PEPT2-/- mice. [14C]GlySar and [14C]5-ALA were studied as a function of temperature, concentration, potential inhibitors, and low sodium conditions.
resultsPEPT2-/- mice exhibited a 90% reduction in GlySar uptake (p < 0.001) and a 92% reduction in 5-ALA uptake (p < 0.001) as compared to wild type animals. At 4 degrees C (vs. 37 degrees C), GlySar uptake was reduced by 95% in PEPT2+/+ mice; no difference was observed in null animals. Unlabeled GlySar inhibited the uptake of [14C]GlySar in PEPT2+/+ mice (p < 0.01); self-inhibition did not occur in PEPT2-/- mice. GlySar demonstrated saturable uptake in PEPT2+/+ mice (Vmax = 16.4 pmol mg(-1) min(-1), Km = 70 microM, Kd = 0.014 microl mg(-1) min(-1)), however, uptake was linear in PEPT2-/- mice (Kd = 0.023 microl mg(-1) min(-1)). Low sodium buffer (1 mM) resulted in 75% and 59% reductions, respectively, in GlySar (p < 0.001) and 5-ALA (p < 0.01) uptake in PEPT2+/+ mice; no differences were observed in PEPT2-/- mice. Overall, about 90-95% of the choroid plexus uptake of GlySar and 5-ALA was mediated by PEPT2, with about 5-10% of the residual uptake occurring by nonspecific mechanisms.
conclusionsThe results demonstrate that PEPT2 is the only transporter responsible for the choroid plexus uptake of GlySar and 5-ALA. They also suggest a role for PEPT2 in the clearance of dipeptides and endogenous peptidomimetics from cerebrospinal fluid.
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