H⁺-linked transport of salicylic acid, an NSAID, in the human trophoblast cell line BeWo

We investigated the transport of salicylic acid and L-lactic acid across the placenta using the human trophoblast cell line BeWo. We performed uptake experiments and measured the change in intracellular pH (pH_i). The uptakes of [¹⁴C] salicylic acid and L-[¹⁴C] lactic acid were temperature- and extracellular pH-dependent and saturable at higher concentrations. Both uptakes were also reduced by FCCP, nigericin, and NaN₃. Various nonsteroidal anti-inflammatory drugs (NSAIDs) strongly inhibited the uptake of L-[¹⁴C] lactic acid. Salicylic acid and ibuprofen noncompetitively inhibited the uptake of L-[¹⁴C] lactic acid. α-Cyano-4-hydroxycinnamate (CHC), a monocarboxylate transporter inhibitor, suppressed the uptake of L-[¹⁴C] lactic acid but not that of [¹⁴C] salicylic acid. CHC also suppressed the decrease of pH_i induced by L-lactic acid but had little effect on that induced by salicylic acid or diclofenac. These results suggest that NSAIDs are potent inhibitors of lactate transporters, although they are transported mainly by a transport system distinct from that for L-lactic acid.