Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract

Elangovan Gopal, Seiji Miyauchi, Pamela Moore Martin, Sudha Ananth, Penny Roon, Sylvia B Smith, Vadivel Ganapathy

Research output: Contribution to journalArticle

67 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)575-584
Number of pages10
JournalPharmaceutical Research
Volume24
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Niacin
Oocytes
Pharmaceutical Preparations
Epithelial Cells
Membranes
Mesalamine
Facings
Volatile Fatty Acids
Salicylates
Benzoates
Intestinal Absorption
Induced currents
Linings
Stoichiometry
Small Intestine
Fluorescent Antibody Technique
Charge transfer
Colon
Fatty Acids
Fluxes

Keywords

  • Aminosalicylates
  • Electrophysiology
  • Intestinal tract
  • Monocarboxylate drugs
  • SMCT1

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract. / Gopal, Elangovan; Miyauchi, Seiji; Martin, Pamela Moore; Ananth, Sudha; Roon, Penny; Smith, Sylvia B; Ganapathy, Vadivel.

In: Pharmaceutical Research, Vol. 24, No. 3, 01.03.2007, p. 575-584.

Research output: Contribution to journalArticle

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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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AU - Martin, Pamela Moore

AU - Ananth, Sudha

AU - Roon, Penny

AU - Smith, Sylvia B

AU - Ganapathy, Vadivel

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N2 - 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.

AB - 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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