Publicação
Thiamine is a substrate of organic cation transporters in Caco-2 cells
| Resumo: | 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. [H-3]-T+ uptake was found to be: 1) time-dependent, 2) Na+- and CI--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 [H-3]-T+ uptake on phosphorylation/dephosphorylation mechanisms was also investigated and [3H]-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 ThTrl 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. |
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| Autores principais: | Clara Lemos |
| Outros Autores: | Ana Faria; Manuela Meireles; Fatima Martel; Rosario Monteiro; Conceicao Calhau |
| Assunto: | Farmacologia clínica, Medicina básica Clinical pharmacology, Basic medicine |
| Ano: | 2012 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade do Porto |
| Idioma: | inglês |
| Origem: | Repositório Aberto da Universidade do Porto |
| Resumo: | 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. [H-3]-T+ uptake was found to be: 1) time-dependent, 2) Na+- and CI--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 [H-3]-T+ uptake on phosphorylation/dephosphorylation mechanisms was also investigated and [3H]-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 ThTrl 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. |
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