PUBLICATION

Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1)

Authors
Popovic, M., Zaja, R., Fent, K., Smital, T.
ID
ZDB-PUB-140805-5
Date
2014
Source
Toxicology and applied pharmacology   280(1): 149-58 (Journal)
Registered Authors
Smital, Tvrtko
Keywords
Lucifer yellow, Oatp1d1, Organic anion transporting polypeptide, environmental chemicals, transport, zebrafish
MeSH Terms
  • Animals
  • Biological Transport/drug effects
  • Biological Transport/physiology
  • Dose-Response Relationship, Drug
  • Environmental Exposure/adverse effects*
  • Environmental Pollutants/metabolism*
  • Environmental Pollutants/toxicity
  • HEK293 Cells
  • Humans
  • Organic Anion Transporters/metabolism*
  • Zebrafish
PubMed
25088042 Full text @ Tox. App. Pharmacol.
CTD
25088042
Abstract
Polyspecific transporters from the Organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl -1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping