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Transport of Nicotinate and Structurally Related Compounds by Human SMCT1 (SLC5A8) and Its Relevance to Drug Transport in the Mammalian Intestinal Tract

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Abstract

Purpose

To examine the involvement of human SMCT1, a Na+-coupled transporter for short-chain fatty acids, in the transport of nicotinate/structural analogs and monocarboxylate drugs, and to analyze its expression in mouse intestinal tract.

Materials and Methods

We expressed human SMCT1 in X. laevis oocytes and monitored its function by [14C]nicotinate uptake and substrate-induced inward currents. SMCT1 expression in mouse intestinal tract was examined by immunofluorescence.

Results

[14C]Nicotinate uptake was several-fold higher in SMCT1-expressing oocytes than in water-injected oocytes. The uptake was inhibited by short-chain/medium-chain fatty acids and various structural analogs of nicotinate. Exposure of SMCT1-expressing oocytes to nicotinate induced Na+-dependent inward currents. Measurements of nicotinate flux and associated charge transfer into oocytes suggest a Na+:nicotinate stoichiometry of 2:1. Monocarboxylate drugs benzoate, salicylate, and 5-aminosalicylate are also transported by human SMCT1. The transporter is expressed in the small intestine as well as colon, and the expression is restricted to the lumen-facing apical membrane of intestinal and colonic epithelial cells.

Conclusions

Human SMCT1 transports not only nicotinate and its structural analogs but also various monocarboxylate drugs. The transporter is expressed on the luminal membrane of the epithelial cells lining the intestinal tract. SMCT1 may participate in the intestinal absorption of monocarboxylate drugs.

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Authors and Affiliations

  1. Departments of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia, 30912, USA

    Elangovan Gopal, Seiji Miyauchi, Pamela M. Martin, Sudha Ananth & Vadivel Ganapathy

  2. Departments of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia, 30912, USA

    Penny Roon & Sylvia B. Smith

Authors
  1. Elangovan Gopal
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  2. Seiji Miyauchi
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  3. Pamela M. Martin
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  4. Sudha Ananth
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  5. Penny Roon
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  7. Vadivel Ganapathy
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Correspondence to Vadivel Ganapathy.

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Gopal, E., Miyauchi, S., Martin, P.M. et al. Transport of Nicotinate and Structurally Related Compounds by Human SMCT1 (SLC5A8) and Its Relevance to Drug Transport in the Mammalian Intestinal Tract. Pharm Res 24, 575–584 (2007). https://doi.org/10.1007/s11095-006-9176-1

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  • DOI: https://doi.org/10.1007/s11095-006-9176-1

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