Butyrate and the other
short-chain fatty acids (SCFAs) are the most abundant
anions in the colonic lumen. Also,
butyrate is the preferred energy source for colonocytes and has been shown to regulate colonic
electrolyte and fluid absorption. Previous studies from our group have demonstrated that the HCO(3)(-)/SCFA(-)
anion exchange process is one of the major mechanisms of
butyrate transport across the purified human colonic apical membrane vesicles and the apical membrane of human colonic
adenocarcinoma cell line Caco-2 and have suggested that it is mainly mediated via monocarboxylate transporter-1 (MCT-1)
isoform. However, little is known regarding the regulation of SCFA transport by various
hormones and signal transduction pathways. Therefore, the present studies were undertaken to examine whether
hydrocortisone and
phorbol 12-myristate 13-acetate (PMA) are involved in a possible regulation of the
butyrate/
anion exchange process in Caco-2 cells. The
butyrate/
anion exchange process was assessed by measuring a pH-driven [(14)C]
butyrate uptake in Caco-2 cells. Our results demonstrated that 24-h incubation with PMA (1 microM) significantly increased [(14)C]
butyrate uptake compared with incubation with 4alphaPMA (inactive form). In contrast, incubation with
hydrocortisone had no significant effect on
butyrate uptake in Caco-2 cells compared with vehicle (
ethanol) alone. Induction of
butyrate uptake by PMA appeared to be via an increase in the maximum velocity (V(max)) of the transport process with no significant changes in the K(m) of the transporter for
butyrate. Parallel to the increase in the V(max) of [(14)C]
butyrate uptake, the MCT-1
protein level was also increased in response to PMA incubation. Our studies demonstrated that the
butyrate/
anion exchange was increased in response to PMA treatment along with the induction in the level of MCT-1 expression in Caco-2 cells.