title: Thiamine is a substrate of organic cation transporters in Caco-2 cells.
abstract: The aim of this study was to characterize the intestinal absorption of thiamine, by investigating the hypothesis of an involvement of Organic Cation Transporter (OCT) family members in this process. [(3)H]-T(+) uptake was found to be: 1) time-dependent, 2) Na(+)- and Cl(-)-dependent, 3) pH-dependent, with uptake increasing with a decrease in extracellular pH and decreasing with a decrease in intracellular pH, 4) inhibited by amiloride, 5) inhibited by the thiamine structural analogues oxythiamine and amprolium, 6) inhibited by the unrelated organic cations MPP(+), clonidine, dopamine, serotonin, 7) inhibited by the OCT inhibitors decynium22 and progesterone. Moreover, the dependence of [(3)H]-T(+) uptake on phosphorylation/dephosphorylation mechanisms was also investigated and [(3)H]-T(+) uptake was found to be reduced by PKA activation and protein tyrosine phosphatase and alkaline phosphatase inhibition. In conclusion, our results are compatible with the possibility of thiamine being transported not only by ThTr1 and/or ThTr2, but also by members of the OCT family of transporters (most probably OCT1 and/or OCT3), thus sharing the same transporters with several other organic cations at the small intestinal level.
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
authors.forename: Clara
authors.initials: C
authors.lastname: Lemos
authors.forename: Ana
authors.initials: A
authors.lastname: Faria
authors.forename: Manuela
authors.initials: M
authors.lastname: Meireles
authors.forename: Fátima
authors.initials: F
authors.lastname: Martel
authors.forename: Rosário
authors.initials: R
authors.lastname: Monteiro
authors.forename: Conceição
authors.initials: C
authors.lastname: Calhau
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000670:Amprolium / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D003891:Desipramine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D010119:Oxythiamine / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D011485:Protein Binding / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D013831:Thiamine / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D027701:Organic Cation Transport Proteins; D005473:Fluoxetine; D010119:Oxythiamine; D012701:Serotonin; D012965:Sodium Chloride; D000584:Amiloride; D010744:Phosphoric Monoester Hydrolases; D000670:Amprolium; D003891:Desipramine; D013831:Thiamine