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

We investigated thetransport of salicylic acid and L-lactic acid across theplacenta using the human trophoblast cell line BeWo. We performeduptake experiments and measured the change in intracellular pH(pH_i). The uptakes of ¹⁴C]salicylic acid andL-¹⁴C]lactic acid were temperature- andextracellular pH-dependent and saturable at higher concentrations. Bothuptakes were also reduced by FCCP, nigericin, and NaN₃.Various nonsteroidal anti-inflammatory drugs (NSAIDs) stronglyinhibited the uptake of L-¹⁴C]lactic acid.Salicylic acid and ibuprofen noncompetitively inhibited the uptake ofL-¹⁴C]lactic acid.-Cyano-4-hydroxycinnamate (CHC), a monocarboxylate transporterinhibitor, suppressed the uptake ofL-¹⁴C]lactic acid but not that of¹⁴C]salicylic acid. CHC also suppressed the decrease ofpH_i induced by L-lactic acid but had littleeffect on that induced by salicylic acid or diclofenac. These resultssuggest that NSAIDs are potent inhibitors of lactate transporters,although they are transported mainly by a transport system distinctfrom that for L-lactic acid.