Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Pharm Res
2006 Jun 01;236:1209-16. doi: 10.1007/s11095-006-0023-1.
Show Gene links
Show Anatomy links
Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8).
Itagaki S, Gopal E, Zhuang L, Fei YJ, Miyauchi S, Prasad PD, Ganapathy V.
???displayArticle.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.
???displayArticle.pubmedLink???
16729224 ???displayArticle.link???Pharm Res
Chen,
Short-chain fatty acid inhibitors of histone deacetylases: promising anticancer therapeutics?
2003,
Pubmed Choi,
Role of monocarboxylic acid transporters in the cellular uptake of NSAIDs.
2005,
Pubmed Coady,
The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter.
2004,
Pubmed
,
Xenbase Ganapathy,
Role of transporters in placental transfer of drugs.
2005,
Pubmed Ganapathy,
Biological functions of SLC5A8, a candidate tumour suppressor.
2005,
Pubmed Ganapathy,
Placental transporters relevant to drug distribution across the maternal-fetal interface.
2000,
Pubmed Ganji,
Niacin and cholesterol: role in cardiovascular disease (review).
2003,
Pubmed Gopal,
Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family.
2005,
Pubmed
,
Xenbase Gopal,
Expression of slc5a8 in kidney and its role in Na(+)-coupled transport of lactate.
2004,
Pubmed
,
Xenbase Gupta,
SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter.
2006,
Pubmed Halestrap,
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.
1999,
Pubmed
,
Xenbase Katsura,
Intestinal absorption of drugs mediated by drug transporters: mechanisms and regulation.
2003,
Pubmed Konstan,
Effect of high-dose ibuprofen in patients with cystic fibrosis.
1995,
Pubmed Li,
SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers.
2003,
Pubmed McKenney,
New perspectives on the use of niacin in the treatment of lipid disorders.
2004,
Pubmed Miyauchi,
Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids.
2004,
Pubmed
,
Xenbase Mizuno,
Impact of drug transporter studies on drug discovery and development.
2003,
Pubmed Mortensen,
Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease.
1996,
Pubmed Peek,
Prevention of colorectal cancer through the use of COX-2 selective inhibitors.
2004,
Pubmed Pereg,
Non-steroidal anti-inflammatory drugs for the prevention and treatment of cancer.
2005,
Pubmed Rodriguez,
Identification and characterization of a putative human iodide transporter located at the apical membrane of thyrocytes.
2002,
Pubmed Rubin,
Physiological disposition of fenoprofen in man. II. Plasma and urine pharmacokinetics after oral and intravenous administration.
1972,
Pubmed Tamai,
Participation of a proton-cotransporter, MCT1, in the intestinal transport of monocarboxylic acids.
1995,
Pubmed
,
Xenbase Velázquez,
Butyrate and the colonocyte. Production, absorption, metabolism, and therapeutic implications.
1997,
Pubmed
