Inhibitory effects of chlorpromazine and diethylaminoethyl diphenylvalerate (SKF 525-A) on alanine incorporation into protein and α-aminoisobutyric acid uptake in rat hepatoma cells in culture

Abstract

Chlorpromazine (CPZ) and SKF 525-A above 0.01 mM inhibit the incorporation of alanine into protein in cultures of a clonal strain of rat hepatoma cells. Fifty per cent inhibition was noted for both drugs at approximately 0.07 mM, and at CPZ 0.15 mM 97 per cent and at SKF 525-A 0.20 mM 96 per cent inhibition respectively was found. Brief washing partially restores normal incorporation rates. CPZ 0.15 mM reduces the amount of total intracellularly accumulated alanine to 11 per cent of controls. The non-metabolizable amino acid α-aminoisobutyric acid (AIB) is actively transported by these cells; CPZ and SKF 525-A inhibit the uptake of AIB, with 44 per cent reduction at a concentration of CPZ 0.15 mM and 55 per cent reduction at SKF 525-A 0.20 mM. The rate of AIB efflux from the cells was also reduced by CPZ 0.15 mM and SKF 525-A 0.20 mM. It is concluded that CPZ and SKF 525-A in a similar pattern inhibit the transport of amino acids in these hepatoma cells in culture.