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Abstractc-jun mRNA levels were increased in rat hepatoma cells (H4-II-E-C3) when exposed to hypotonic medium (205 mosmol/l) with a maximal induction observed after 1 h of hypotonic exposure. At this time point an approximate 5-fold increase in c-jun expression could be detected in relation to normotonic control incubations (305 mosmol/l). Hypertonic exposure (405 mosmolll) had only a slight effect on c-jun expression. In contrast to the increased c-jun mRNA levels under hypotonic conditions, expression of the c-j&r proto-oncogene was unaffected by changes in the osmolarity. The hypotonicity-induced increase in c-jun expression was also detectable in the presence of a protein kinase C (PKC) inhibitor. This indicates that PKC is not involved in the signal transduction pathway leading to c-jun expression upon hypotonic cell swelling in these cells.

Exposure of isolated perfused rat livers to hypo-osmotic (225 mosmol/l) perfusion media for 3 h led to a decrease of about 60% in mRNA levels for phosphoenolpyruvate carboxy-kinase (PEPCK) compared with normo-osmotic (305 mosmol/l) perfusions. Conversely, PEPCK mRNA levels increased about 3-fold during hyperosmotic (385 mosmol/l) perfusions. The anisotonicity effects were not explained by changes in the intracellular cyclic AMP (cAMP) concentration or by changes of the extracellular Na+ or Cl- activity. Similar effects of aniso-osmolarity on PEPCK mRNA levels were found in cultured rat hepatoma H4IIE.C3 cells, the experimental system used for further characterization of the effect. Whereas during the first hour of anisotonic exposure no effects on PEPCK mRNA levels were detectable, near-maximal aniso-osmolarity effects were observed within the next 2-3 h. PEPCK mRNA levels increased sigmoidally with the osmolarity of the medium, and the anisotonicity effects were most pronounced upon modulation of osmolarity between 250 and 350 mosmol/l. The aniso-osmolarity effects on PEPCK mRNA were not affected in presence of Gö 6850, protein kinase C inhibitor. cAMP increased the PEPCK mRNA levels about 2.3-fold in normo-osmotic media, whereas insulin lowered the PEPCK mRNA levels to about 8%. The effects of cAMP and insulin were also observed during hypo-osmotic and hyperosmotic exposure, respectively, but the anisotonicity effects were not abolished in presence of the hormones. The data suggest that hepatocellular hydration affects hepatic carbohydrate metabolism also over a longer term by modulating PEPCK mRNA levels. This is apparently unrelated to protein kinase C or alterations of cAMP levels. The data strengthen the view that cellular hydration is an important determinant for cell metabolic function by extending its regulatory role in carbohydrate metabolism to the level of mRNA.