Modulation of butyrate transport in Caco-2 cells

• Tipo: Artigo em Revista Científica Internacional
• Data: 2009

Autores

Gonçalves P (Autor) FMUP; Araújo JR (Autor) FMUP; Maria João Pinho (Autor) FMUP; Martel, F (Autor) FMUP

Revista

Título: Naunyn-Schmiedeberg's Archives of Pharmacology

Vol. 379

Páginas: 325-336

ISSN: 0028-1298

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 27 Citações

Scopus - 32 Citações

Outras Informações

ID Authenticus: P-003-M9C

DOI: 10.1007/s00210-008-0372-x

Abstract (EN): 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 (14)C-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, alpha-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 (14)C-BT (10 mu M) 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 (14)C-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 (14)C-BT uptake. Acetylsalicylic acid simultaneously increased the Km and the V(max) of (14)C-BT uptake. In conclusion, MCT1-mediated transport of (14)C-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).

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12