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


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 SMCTI. 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 SMCTI 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.
Gopal
Elangovan
E
Department of Biochemistry, Medical College of Georgia, Augusta, Georgia 30912, USA.
Miyauchi
Seiji
S
Martin
Pamela M
PM
Ananth
Sudha
S
Roon
Penny
P
Smith
Sylvia B
SB
Ganapathy
Vadivel
V
D000636:Aminosalicylic Acids / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D041741:Lower Gastrointestinal Tract / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D027501:Monocarboxylic Acid Transporters / Q000502:physiology; D009525:Niacin / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology; D014316:Tritium; D014982:Xenopus laevis
D000636:Aminosalicylic Acids; D001565:Benzoates; D027682:Cation Transport Proteins; D027501:Monocarboxylic Acid Transporters; C476760:SLC5A8 protein, human; D014316:Tritium; D009525:Niacin; D012965:Sodium Chloride