Purpose  

Sodium-coupled monocarboxylate transporter 1 (SMCT1) is a Na⁺-coupled transporter for monocarboxylates. Many nonsteroidal anti-inflammatory drugs (NSAIDs) are monocarboxylates. Therefore, we investigated the interaction of these drugs with human SMCT1 (hSMCT1).

Methods  

We expressed hSMCT1 in a mammalian cell line and in Xenopus laevis oocytes and used the uptake of nicotinate and propionate-induced currents to monitor its transport function, respectively. We also used [¹⁴C]-nicotinate and [³H]-ibuprofen for direct measurements of uptake in oocytes.

Results  

In mammalian cells, hSMCT1-mediated nicotinate uptake was inhibited by ibuprofen and other structurally related NSAIDs. The inhibition was Na⁺ dependent. With ibuprofen, the concentration necessary for 50% inhibition was 64 ± 16 μM. In oocytes, the transport function of hSMCT1 was associated with inward currents in the presence of propionate. Under identical conditions, ibuprofen and other structurally related NSAIDs failed to induce inward currents. However, these compounds blocked propionate-induced currents. With ibuprofen, the blockade was dose dependent, Na⁺ dependent, and competitive. However, there was no uptake of [³H]-ibuprofen into oocytes expressing hSMCT1, although the uptake of [¹⁴C]-nicotinate was demonstrable under identical conditions.

Conclusions  

Ibuprofen and other structurally related NSAIDs interact with hSMCT1 as blockers of its transport function rather than as its transportable substrates.