Inhibition of the expression of the "A" system of amino acid transport by anti-inflammatory drugs during cell culture growth and mitogenic stimulation of thymus lymphocytes.

alpha-Methylaminoisobutyric acid uptake is mediated by two components in a variety of cell culture lines as well as in freshly isolated thymus lymphocytes. In all cell types, one component of uptake had characteristics similar to that of the "A" system and was selectively inhibited by the nonsteroidal anti-inflammatory drugs. Detailed studies with indomethacin showed that, in the presence of drug, a marked decrease in Vmax occurred with no impairment in the apparent affinity (Km) of the uptake system for either the amino acid or Na+ ion. Upon removal of drug, the capacity (Vmax) of the cell lines to take up amino acid recovered over the course of 6 hr. It is postulated that this time course may be related to a change in the number of functional carriers in the cell membrane. Marked increases in the rate of alpha-methylaminoisobutyric acid uptake by the Na+-dependent component were observed during exponential growth of cell cultures and in thymus lymphocytes stimulated by concanavalin A or amino acid deprivation. Irrespective of the cell type or mechanism of stimulation, indomethacin either blocked or partially suppressed this increase. Suppression of the Na+-dependent component of alpha-methylaminoisobutyric acid uptake was also evident in lymphocytes from indomethacin-treated rats. Selective inhibition of the A system before DNA synthesis may be one mechanism by which the anti-inflammatory drugs exert their in vitro cytostatic and in vivo immunosuppressive action