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Modulation of butyrate transport in Caco-2 cells

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Abstract

The aim of this study was to investigate the putative influence of some pharmacological agents and drugs of abuse upon the apical uptake of butyrate (BT) into Caco-2 cells. The apical uptake of 14C-BT by Caco-2 cells was (1) time and concentration dependent, (2) pH dependent, (3) Na+ independent and Cl− dependent, (4) energy dependent, (5) inhibited by several BT structural analogues (acetate, propionate, α-ketobutyrate, pyruvate, lactate), (6) insensitive to the anion exchange inhibitors DIDS and SITS and (7) inhibited by the monocarboxylate transport (MCT) inhibitors NPPB and pCMB. These characteristics are compatible with an involvement of MCT1-mediated transport. Acutely, uptake of a low concentration of 14C-BT (10 μM) was reduced by acetaldehyde, acetylsalicylic acid, indomethacin, caffeine and theophylline and increased by MDMA. Chronically, uptake was increased by caffeine and decreased by tetrahydrocannabinol and MDMA; reverse transcription quantitative real-time PCR analysis showed that these three compounds decreased the mRNA levels of MCT1. Acutely, acetaldehyde, indomethacin and MDMA reduced the uptake of a high concentration of 14C-BT (20 mM), and acetylsalicylic acid increased it. Chronically, none of the compounds affected uptake. Acetaldehyde, indomethacin and propionate seem to be competitive inhibitors of 14C-BT uptake. Acetylsalicylic acid simultaneously increased the K m and the V max of 14C-BT uptake. In conclusion, MCT1-mediated transport of 14C-BT in Caco-2 cells is modulated by either acute or chronic exposure to some pharmacological agents and drugs of abuse (acetaldehyde, acetylsalicylic acid, indomethacin, caffeine, theophylline and the drugs of abuse tetrahydrocannabinol and MDMA).

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Acknowledgements

This work was supported by Fundação para a Ciência e a Tecnologia (FCT) and Programa Ciência, Tecnologia e Inovação do Quadro Comunitário de Apoio (PTDC/SAU-FCF/67805/2006). The authors wish to thank Prof. Isabel Azevedo for the revision of the manuscript.

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  1. Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, 4200-319, Porto, Portugal

    Pedro Gonçalves, João Ricardo Araújo & Fátima Martel

  2. Institute of Pharmacology and Therapeutics (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal

    Maria João Pinho

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  1. Pedro Gonçalves
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Gonçalves, P., Araújo, J.R., Pinho, M.J. et al. Modulation of butyrate transport in Caco-2 cells. Naunyn-Schmied Arch Pharmacol 379, 325–336 (2009). https://doi.org/10.1007/s00210-008-0372-x

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