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

Shirou Itagaki, Elangovan Gopal, Lina Zhuang, You Jun Fei, Seiji Miyauchi, Puttur D Prasad, Vadivel Ganapathy

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 μM. 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.

Original languageEnglish (US)
Pages (from-to)1209-1216
Number of pages8
JournalPharmaceutical Research
Volume23
Issue number6
DOIs
StatePublished - Jun 1 2006

Fingerprint

Ibuprofen
Anti-Inflammatory Agents
Sodium
Niacin
Oocytes
Pharmaceutical Preparations
Propionates
Induced currents
Cells
Xenopus laevis
Drug Interactions
Cell Line
Substrates

Keywords

  • Blocker
  • Electrophysiology
  • Ibuprofen
  • SMCT1
  • Sodium dependence

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8). / Itagaki, Shirou; Gopal, Elangovan; Zhuang, Lina; Fei, You Jun; Miyauchi, Seiji; Prasad, Puttur D; Ganapathy, Vadivel.

In: Pharmaceutical Research, Vol. 23, No. 6, 01.06.2006, p. 1209-1216.

Research output: Contribution to journalArticle

Itagaki, Shirou ; Gopal, Elangovan ; Zhuang, Lina ; Fei, You Jun ; Miyauchi, Seiji ; Prasad, Puttur D ; Ganapathy, Vadivel. / Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8). In: Pharmaceutical Research. 2006 ; Vol. 23, No. 6. pp. 1209-1216.
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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 μM. 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.",
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author = "Shirou Itagaki and Elangovan Gopal and Lina Zhuang and Fei, {You Jun} and Seiji Miyauchi and Prasad, {Puttur D} and Vadivel Ganapathy",
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T1 - Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8)

AU - Itagaki, Shirou

AU - Gopal, Elangovan

AU - Zhuang, Lina

AU - Fei, You Jun

AU - Miyauchi, Seiji

AU - Prasad, Puttur D

AU - Ganapathy, Vadivel

PY - 2006/6/1

Y1 - 2006/6/1

N2 - 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 μM. 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.

AB - 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 μM. 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.

KW - Blocker

KW - Electrophysiology

KW - Ibuprofen

KW - SMCT1

KW - Sodium dependence

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M3 - Article

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VL - 23

SP - 1209

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JF - Pharmaceutical Research

SN - 0724-8741

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