Different transporters for tri-iodothyronine (T(3)) and thyroxine (T(4)) in the human choriocarcinoma cell line, JAR.
We investigated transport systems for tri-iodothyronine (T(3)) and thyroxine (T(4)) in the human choriocarcinoma cell line, JAR, using a range of structurally similar compounds to determine whether these thyroid hormones are transported by common or different mechanisms. Saturable T(3) but not saturable T(4) uptake was inhibited by a wide range of aromatic compounds (nitrendipine, nifedipine, verapamil, meclofenamic acid, mefenamic acid, diazepam, phenytoin). Nitrendipine and diazepam were the most effective inhibitors of saturable thyroid hormone uptake. Nitrendipine decreased the K(m) for T(4) uptake from a control value of around 500 nM to around 300 nM (n=6). In contrast, the K(m) for T(3) uptake was increased from a control value of around 300 nM to around 750 nM (n=4). Diazepam had similar effects. This divergent shift in affinity for the uptake of T(3) and T(4) suggested that separate uptake systems exist for these two thyroid hormones. This provides evidence for at least two transporters mediating uptake of T(3) and T(4) in JAR cells: a specific T(4) transporter that does not interact with T(3) or structurally similar compounds; and a shared iodothyronine transporter that interacts with T(3), T(4), nitrendipine and diazepam.
Powell
K A
KA
Conjoint Endocrine Laboratory, Royal Brisbane Hospital Research Foundation, The Bancroft Centre, 300 Herston Road, Brisbane, Queensland 4029, Australia. kellieP@qimr.edu.au
Mitchell
A M
AM
Manley
S W
SW
Mortimer
R H
RH
Mortimer
R H
RH
D000704:Analysis of Variance; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002822:Choriocarcinoma / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D007930:Leucine / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D008528:Mefenamic Acid / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D010649:Phenylalanine / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D013974:Thyroxine / Q000493:pharmacokinetics*; D014284:Triiodothyronine / Q000493:pharmacokinetics*; D014364:Tryptophan / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D018757:GABA Modulators; D007457:Iodine Radioisotopes; D014284:Triiodothyronine; D008528:Mefenamic Acid; D010649:Phenylalanine; D008469:Meclofenamic Acid; D010672:Phenytoin; D014364:Tryptophan; D009568:Nitrendipine; D014700:Verapamil; D007930:Leucine; D009543:Nifedipine; D003975:Diazepam; D013974:Thyroxine