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 struct urally similar compounds to determine whether these thyroid hormones are tr ansported by common or different mechanisms. Saturable T-3 but not saturabl e T-4 uptake was inhibited by a wide range of aromatic compounds (nitrendip ine, nifedipine, verapamil, meclofenamic acid, mefenamic acid, diazepam, ph enytoin). Nitrendipine and diazepam were the most effective inhibitors of saturable t hyroid 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, K-m T-3 uptake was increased from a control value of around 300 nM to around 75 0 nM (n = 4). Diazepam had a similar effects. This divergent shift in affin ity for the uptake of T-3 and T-4 suggested that separate uptake systems ex ist 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 w ith T-3 or structurally similar compounds; and a shared idothyronine transp orter that interacts with T-3, T-4, nitrendipine and diazepam.