Glutamine increases argininosuccinate synthetase mRNA levels in rat hepatocytes. The involvement of cell swelling.

Glutamine, one of the most efficient substrates in the urea cycle, was found to induce the accumulation of argininosuccinate synthetase (ASS) mRNA in primary cultured rat hepatocytes. The inducing action of glutamine was obtained at various stages of development and a half-maximal effect was observed at about 3 mM glutamine. This effect was apparent from 6 h and persisted for at least 48 h. NH4Cl addition up to 5 mM did not significantly change the ASS mRNA level. Like glutamine, hypoosmotic medium and aminoisobutyric acid (conditions known to increase cell volume) also increased the ASS mRNA level, which was, in contrast, decreased by hyperosmotic medium. These results demonstrate that the glutamine-induced swelling may participate in the observed increase of the ASS mRNA level. This increase in the ASS mRNA level was associated with an increase in ASS activity.