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

doi:10.1007/s11095-006-0023-1

Cited by 43 publications

(31 citation statements)

References 25 publications

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“…High dose propionate had a significant effect on the expression of SMCT1, which is consistent with Itagaki's work. 47) The direct effects of acarbose and voglibose on Caco-2 cells were different from each other, and voglibose seemed to have no significant effect on epithelial cells while acarbose significantly decreased the expression of SMCT1, SGLT1 and GLUT2, and this is not similar to the results reported previously. 32) The differences may be attributed to different carriers, the work was carried out in vivo but Caco-2 cells were stimulated directly with acarbose and voglibose in this study.…”

Section: Discussioncontrasting

confidence: 66%

Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after Exposure of Two Glycosidase Inhibitors in Mice

Cai

et al. 2018

Biological & Pharmaceutical Bulletin

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Acarbose and voglibose are the most widely used diabetes drugs as glycosidase inhibitors. In this study, the use of these two inhibitors significantly increased the content of starch in large intestine, and altered the concentration of short-chain fatty acids (SCFAs) by affecting the intestinal microbiota. However, there are some differences in the intestinal microbiome of the two groups of mice, mainly in bacteria such as Bacteroidaceae bacteroides and Desulfovibrionaceae desulfovibrio. The productions of acetate and propionate in caecum in voglibose group were significantly higher than those in acarbose group and two kinds of glycosidase inhibitors were close in the production of butyrate in caecum. The Tax4Fun analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data indicated that different productions of acetate and propionate between acarbose group and voglibose group may be related to 2-oxoisovalerate dehydrogenase and pyruvate oxidase. In addition, in-vitro experiments suggested that voglibose had less effect on epithelial cells than acarbose after direct stimulation. According to the recent researches of SCFAs produced by intestinal microbiota, our comparative study shown higher concentration of these beneficial fatty acids in the lumen of voglibose-treated mice, which implied a lower level of inflammation.Key words acarbose; voglibose; microbiota; short-chain fatty acid; Tax4FunWith the increasing number of obesity and diabetes around the world, there are more and more different classes of medications to treat diabetes, such as biguanides (metformin), sulfonylureas, insulin, glucagon-like peptide 1 (GLP-1) agonists, dipeptidyl peptidase IV inhibitors, thiazolidinediones and sodium-glucose transporter 2 inhibitors (to name a few). 1) However, acarbose and voglibose as part of α-glucosidase inhibitors (AGIs) are another class of anti-diabetic medications. As first-line hypoglycemic drugs used in patients with type 2 diabetes especially in Asian since their diet meals contain high content of carbohydrates, acarbose and voglibose can typically reduce postprandial glucose level by delaying carbohydrate digestion in the gut, so they can be a useful treatment in the patients who raised basal glucose concentrations slightly and marked postprandial hyperglycemia. 2) In addition, there will also be some side effects, mainly reflected in gastrointestinal flatulence, loose stool and so on. The main reason for this is that fermentation of undigested carbohydrates by bacteria produced gas in the colon. 3) Acarbose and voglibose treatment delayed starch digestion in the small intestine but there was compensatory salvage through bacterial fermentation in the large intestine. 4) When carbohydrates (starch, dietary fiber) enter the large intestine, they are degraded by the fermentation of anaerobic flora. 5) Under normal diet situations, the better part of starch was digested and absorbed in the small intestine, therefore, extra starch entering the large bowel changed microbial eco-system to some degree. Som...

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Section: Discussioncontrasting

confidence: 66%

Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after Exposure of Two Glycosidase Inhibitors in Mice

Cai

et al. 2018

Biological & Pharmaceutical Bulletin

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“…The kinetic parameters were determined using SigmaPlot software (version 10; Systat Software, Chicago, IL). The effect of ibuprofen, an inhibitor of SLC5A8, 31 on SLC5A8-mediated MMF transport was also studied. The dose-response relationship for ibuprofen-induced inhibition of MMFinduced currents in these oocytes was investigated by fitting the data to the Michaelis-Menten equation, which enabled us to determine the value for K 0.5 (i.e., the concentration of ibuprofen necessary to cause 50% maximal inhibition of MMF-induced currents).…”

Section: Transport Of Mmf Via Human Slc5a8 In the Xenopus Laevis Oocymentioning

confidence: 99%

“…As an additional means of confirming that MMF is in fact a transportable substrate for SLC5A8, studies were conducted also in the presence of ibuprofen, a blocker of human SLC5A8. 31 If MMF is truly a transportable substrate for SLC5A8, then the addition of ibuprofen to the perifusion medium should interfere with MMF-induced inward currents in SLC5A8-expressing oocytes. To test this, we monitored inward currents in SLC5A8-expressing oocytes perifused with MMF (1 mM) in the presence of Na þ and increasing concentrations of ibuprofen.…”

Section: Influence Of Various Fumaric Acid Esters On System X C à Actmentioning

confidence: 99%

Induction of the Cystine/Glutamate Exchanger SLC7A11 in Retinal Pigment Epithelial Cells by the Antipsoriatic Drug Monomethylfumarate

Ananth

Babu²,

Veeranan-Karmegam

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…Potential substrates of SLC5A8 with pharmacological relevance include salicylates, benzoate, and non-steroidal anti-inflammatory drugs. Therefore, we examined the interaction of these monocarboxylates with SLC5A8 (16,35). These studies have shown that benzoate, salicylate, and 5-aminosalicylate are transported via SLC5A8.…”

Section: Relevance Of Slc5a8 To Drug Transportmentioning

confidence: 99%

“…The Michaelis constant for these drugs is in the range of 1-7 mM. In contrast to these drugs, non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen interact with the transporter but do not serve as transportable substrates (35). Ibuprofen is able to block the transport function of SLC5A8 by competing with transportable substrates such as lactate, nicotinate, and short-chain fatty acids, but is not transported.…”

Section: Relevance Of Slc5a8 To Drug Transportmentioning

confidence: 99%

Sodium-coupled Monocarboxylate Transporters in Normal Tissues and in Cancer

Ganapathy

Thangaraju

Gopal

et al. 2008

AAPS J

Self Cite

202

187

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Abstract. SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na + -coupled manner. They are expressed in the gastrointestinal tract, kidney, thyroid, brain, and retina. SLC5A8 is localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to neurons and the retinal pigment epithelium. The physiologic functions of SLC5A8 include absorption of short-chain fatty acids in the colon and small intestine, reabsorption of lactate and pyruvate in the kidney, and cellular uptake of lactate and ketone bodies in neurons. It also transports the B-complex vitamin nicotinate. SLC5A12 is also localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to astrocytes and Müller cells. SLC5A8 also functions as a tumor suppressor; its expression is silenced in tumors of colon, thyroid, stomach, kidney, and brain. The tumor-suppressive function is related to its ability to mediate concentrative uptake of butyrate, propionate, and pyruvate, all of which are inhibitors of histone deacetylases. SLC5A8 can also transport a variety of pharmacologically relevant monocarboxylates, including salicylates, benzoate, and g-hydroxybutyrate. Non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen, also interact with SLC5A8. These drugs are not transportable substrates for SLC5A8, but instead function as blockers of the transporter. Relatively less is known on the role of SLC5A12 in drug transport.

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Interaction of Ibuprofen and Other Structurally Related NSAIDs with the Sodium-Coupled Monocarboxylate Transporter SMCT1 (SLC5A8)

Abstract: Ibuprofen and other structurally related NSAIDs interact with hSMCT1 as blockers of its transport function rather than as its transportable substrates.

Cited by 43 publications

References 25 publications

Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after Exposure of Two Glycosidase Inhibitors in Mice

Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after Exposure of Two Glycosidase Inhibitors in Mice

Induction of the Cystine/Glutamate Exchanger SLC7A11 in Retinal Pigment Epithelial Cells by the Antipsoriatic Drug Monomethylfumarate

Sodium-coupled Monocarboxylate Transporters in Normal Tissues and in Cancer

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