title: Mammalian colonocytes possess a carrier-mediated mechanism for uptake of vitamin B3 (niacin): studies utilizing human and mouse colonic preparations.
abstract: Niacin (vitamin B3; nicotinic acid) plays an important role in maintaining redox state of cells and is obtained from endogenous and exogenous sources. The latter source has generally been assumed to be the dietary niacin, but another exogenous source that has been ignored is the niacin that is produced by the normal microflora of the large intestine. For this source of niacin to be bioavailable, it needs to be absorbed, but little is known about the ability of the large intestine to absorb niacin and the mechanism involved. Here we addressed these issues using the nontransformed human colonic epithelial NCM460 cells, native human colonic apical membrane vesicles (AMV) isolated from organ donors, and mouse colonic loops in vivo as models. Uptake of ³H-nicotinic acid by NCM460 cells was: 1) acidic pH (but not Na⁺) dependent; 2) saturable (apparent Km = 2.5 ± 0.8 μM); 3) inhibited by unlabeled nicotinic acid, nicotinamide, and probenecid; 4) neither affected by other bacterially produced monocarboxylates, monocarboxylate transport inhibitor, or by substrates of the human organic anion transporter-10; 5) affected by modulators of the intracellular protein tyrosine kinase- and Ca²⁺-calmodulin-regulatory pathways; and 6) adaptively regulated by extracellular nicotinate level. Uptake of nicotinic acid by human colonic AMV in vitro and by mouse colonic loops in vivo was also carrier mediated. These findings report, for the first time, that mammalian colonocytes possess a high-affinity carrier-mediated mechanism for nicotinate uptake and show that the process is affected by intracellular and extracellular factors.
authors.affiliation: Department of Medicine, University of California, Irvine, CA, USA.
authors.forename: Jeyan S
authors.initials: JS
authors.lastname: Kumar
authors.forename: Veedamali S
authors.initials: VS
authors.lastname: Subramanian
authors.forename: Rubina
authors.initials: R
authors.lastname: Kapadia
authors.forename: Moti L
authors.initials: ML
authors.lastname: Kashyap
authors.forename: Hamid M
authors.initials: HM
authors.lastname: Said
mesh_terms: D000818:Animals; D001682:Biological Availability; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors; D009525:Niacin / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects; D014316:Tritium
chemical_list: D002147:Calmodulin; D002264:Carboxylic Acids; D002352:Carrier Proteins; D027501:Monocarboxylic Acid Transporters; D014316:Tritium; D009536:Niacinamide; D009525:Niacin; D011505:Protein-Tyrosine Kinases; D011339:Probenecid; D002118:Calcium
keywords: colonic uptake; human organic anion transporter-10; microbiota; nicotinic acid; transport