INHIBITION OF THE H+ PEPTIDE COTRANSPORTER IN THE HUMAN INTESTINAL-CELL LINE CACO-2 BY CYCLIC-AMP/

Treatment of Caco-2 cells with cholera toxin inhibits the activity of the H+/peptide cotransporter. The effect of cholera toxin is mimicked by E. coli heat-labile enterotoxin, forskolin and isobutylmethylxanthi ne and is associated with an increase in cAMP levels in the cells. The inhibition is due to a decrease in the maximal velocity of the transp ort system. Inhibitors of protein kinase A and protein kinase C block the effect of cholera toxin. Interestingly, the H+/peptide cotransport er in Caco-2 cells does not possess any putative site for phosphorylat ion by protein kinase A but does possess sites for phosphorylation by protein kinase C. It appears that the cAMP-dependent inhibition of the H+/peptide cotransporter in Caco-2 cells is mediated through activati on of protein kinase C. (C) 1996 Academic Press, Inc.