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 extr acellular amino acids by fetal lung fibroblasts was examined. RA decre ased the incorporation of [H-3]proline into collagen and other protein s. The effect was maximal at a RA concentration of 10(-5) M; smaller d ecreases were observed at a RA concentration of 10(-6) M. This decreas e in collagen formation was associated with a large decrease in intrac ellular [H-3] proline. The decrease in intracellular [H-3]proline was first observed at 2 h following the addition of RA to cell cultures. T ransport studies employing radiolabeled amino acids revealed that RA d ecreased the uptake of proline, 2-aminoisobutyric acid, and 2-(methyla mino) isobutyric acid but not leucine or methionine. Kinetic analysis of 2-aminoisobutyric acid uptake indicated that this effect was mediat ed primarily by an increase in apparent K(m), with a lesser decrease i n V(max). 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 alteri ng the function of the Na+-dependent A transport system for amino acid uptake.