Amino acid activation of amino acid transport System N early in primary cultures of rat hepatocytes.

System N, a neutral amino acid transport system characterized in rat hepatocytes, shows significant changes in activity during the first 24 hr of primary culture (Weissbach, L., Handlogten, M.E., Christensen, H.N., and Kilberg, M.S. [1982] J. Biol. Chem. 257:12006-12011). Experiments presented in the present report demonstrate that during the first 12 hr of primary culture System N can be stimulated by individual amino acids in the culture medium by a cycloheximide-insensitive mechanism. This enhanced activity results from an elevation in the Vmax of the transport system, and the magnitude of the increase is related to the concentration of the amino acid in the culture medium. Nonsubstrates as well as substrates of System N are effective, and trans-stimulation does not appear to play a role in this phenomena. Transport by Systems ASC, Gly, and L is enhanced by the presence of amino acids in the culture medium, but these systems are significantly less sensitive than System N. The results suggest that amino acids act at a posttranslational step to activate System N activity.