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1 Section of Digestive and Liver Diseases, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; West Side VA Medical Center, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: pkdudeja{at}uic.edu.
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 HCO3-/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, Caco2, and suggested that it is mainly mediated via monocarboxylate transporter MCT-1 isoform. However, little is known regarding the regulation of SCFA transport by various hormones and signal transduction pathways. Therefore, the current studies were undertaken to examine whether hydrocortisone and phorbol ester, PMA are involved in a possible regulation of butyrate/anion exchange process in Caco2 cells. Butyrate/anion exchange process was assessed by measuring a pH-driven 14C-butyrate uptake in Caco2 cells. Our results demonstrated that 24 h
incubation with PMA (1 µM) significantly increased 14C-butyrate uptake compared to incubation with 4
PMA (inactive form). In contrast, incubation with hydrocortisone had no significant effect on butyrate uptake in Caco2 cells compared to vehicle (ethanol) alone. The induction of butyrate uptake by PMA appeared to be via an increase in the Vmax of the transport process with no significant changes in the Km of the transporter for butyrate. Parallel to the increase in the Vmax of 14C-butyrate uptake, 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 MCT1 expression in Caco2 cells.
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