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

1 Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences,. and 3 Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582; and 2 Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka 814-0193, Japan 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 [ 14 C]salicylic acid and L -[ 14 C]lactic acid were temperature- and extracellular pH-dependent and saturable at higher concentrations. Both uptakes were also reduced by FCCP, nigericin, and NaN 3 . Various nonsteroidal anti-inflammatory drugs (NSAIDs) strongly inhibited the uptake of L -[ 14 C]lactic acid. Salicylic acid and ibuprofen noncompetitively inhibited the uptake of L -[ 14 C]lactic acid. -Cyano-4-hydroxycinnamate (CHC), a monocarboxylate transporter inhibitor, suppressed the uptake of L -[ 14 C]lactic acid but not that of [ 14 C]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. L -lactic acid; blood-placental barrier; monocarboxylate transporter; -cyano-4-hydroxycinnamate; intracellular pH