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Am J Physiol Cell Physiol (December 19, 2001). doi:10.1152/ajpcell.00179.2001
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Articles in PresS, published online ahead of print December 19, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00179.2001
Submitted on April 17, 2001
Accepted on December 17, 2001

H+-Linked transport of salicylic acid, an NSAIDs, in human trophoblast cell line, BeWo

Emoto Akiko1, Ushigome Fumihiko1, Koyabu Noriko1, Kajiya Hiroshi2, Okabe Koji2, Satoh Shoji3, Tsukimori Kiyomi3, Nakano Hitoo3, Ohtani Hisakazu1, and Sawada Yasufumi1*

1 Medico-Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan
2 Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Fukuoka, Japan
3 Reproduction and Gynecology, Kyushu University, Fukuoka, Fukuoka, Japan

* To whom correspondence should be addressed. E-mail: sawada{at}phar.kyushu-u.ac.jp.

We investigated the transport of salicylic acid and L-lactic acid across the placenta using human trophoblast cell line, BeWo. We performed uptake experiments and measured the change in intracellular pH. The uptakes of [14C]salicylic acid and [14C]L-lactic acid, were temperature-, extracellular pH-dependent and saturable at higher concentration. Both uptakes were also reduced by FCCP, nigericin and NaN3. Various nonsteroidal anti-inflammatory drugs (NSAIDs) strongly inhibited the uptake of [14C]L-lactic acid. Salicylic acid and ibuprofen non-competitively inhibited the uptake of [14C]L-lactic acid. {alpha}-Cyano-4-hydroxycinnamate (CHC), a monocarboxylate transporter (MCT) inhibitor, suppressed the uptake of [14C]L-lactic acid, but not that of [14C]salicylic acid. CHC also suppressed the decrease of intracellular pH 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, while they are transported mainly by a transport system distinct from that for L-lactic acid.




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