Effects of phenothiazines on phosphate incorporation and chloride uptake in isolated intestinal epithelial cells

Isolated, intact epithelial cells from rat ileum synthesized a variety of radiolabeled compounds when 32Pi was added to the incubation medium. One of these, referred to as P-0.7 because of its Rf value in the thin layer chromatography system used to separate phosphorylated compounds, was found in the extracellular medium but not in extracts of cells. Synthesis of P-0.7 was inhibited by phenothiazines, with an EC50 value of 205 microM for trifluoperazine. Phenothiazines also inhibited uptake into isolated cells, with EC50 values of 288 and 359 microM for trifluoperazine and chlorpromazine, respectively. Effects of the phenothiazines on chloride uptake were not mimicked by the local anesthetic lidocaine (1 mM), the calcium channel blocker verapamil (0.5 mM), SITS or furosemide, or by removal of sodium or calcium from the medium.