The effect of retinoic acid on amino acid uptake and protein synthesis by lung fibroblasts

The effect of retinoic acid (RA) on the uptake and utilization of extracellular amino acids by fetal lung fibroblasts was examined. RA decreased the incorporation of 3H]proline into collagen and other proteins. The effect was maximal at a RA concentration of 10(-5) M; smaller decreases were observed at a RA concentration of 10(-6) M. This decrease in collagen formation was associated with a large decrease in intracellular 3H] proline. The decrease in intracellular 3H]proline was first observed at 2 h following the addition of RA to cell cultures. Transport studies employing radiolabeled amino acids revealed that RA decreased the uptake of proline, 2-aminoisobutyric acid, and 2-(methylamino)isobutyric acid but not leucine or methionine. Kinetic analysis of 2-aminoisobutyric acid uptake indicated that this effect was mediated primarily by an increase in apparent Km, with a lesser decrease in Vmax, RA-induced inhibition of proline uptake was not abolished by the presence of cycloheximide nor by pretreatment with indomethacin. Na+,K(+)-ATPase activity was not affected by RA treatment. These results suggest that RA modulates protein production in fibroblasts by altering the function of the Na(+)-dependent A transport system for amino acid uptake.