Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8).

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Citation

Itagaki S, Gopal E, Zhuang L, Fei YJ, Miyauchi S, Prasad PD, Ganapathy V

Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8).

Pharm Res. 2006 Jun;23(6):1209-16. Epub 2006 Jun 1.

PubMed ID
16729224 [ View in PubMed
]
Abstract

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 microM. 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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Sodium-coupled monocarboxylate transporter 1Q8N695Details