3-Iodothyronamine (T(1)AM) is a naturally occurring thyroid hormone metabolite 
with distinct biological effects that are opposite those of thyroid hormone. The 
known molecular targets of T(1)AM include both plasma membrane and intracellular 
proteins, suggesting that intracellular transport of T(1)AM may be an important 
component of its action, although no uptake mechanism has yet been described. 
Using various human cell lines, we show that, indeed, cellular uptake of T(1)AM 
occurs in multiple cell types and that this process involves specific, 
saturable, and inhibitable transport mechanisms. These mechanisms are sodium and 
chloride independent, pH dependent, thyronamine specific, and do not involve the 
likely candidate transporters of other monoamines, organic cations, or thyroid 
hormones. A large-scale RNA interference screen targeting the entire solute 
carrier superfamily of transporter genes reveals that the transport of T(1)AM 
into cells involves multiple transporters, and we identify eight transporters 
that may contribute to the uptake of T(1)AM in HeLa cells. This type of 
transporter small interfering RNA screening approach can be used in general to 
identify the constellation of transporters that participate in the intracellular 
disposition of compounds.