Augmentation of urea-synthetic capacity by inhibition of nitric oxide synthesis in butyrate-induced differentiated human hepatocytes.

We have recently developed an in vitro differentiation model of immortalized non-transformed human hepatocytes using butyrate, and observed the induction of inducible NO synthase (iNOS). In this study, we analyzed the effect of NO on the urea-synthetic capacity of these cells. The inhibition of iNOS during butyrate treatment significantly increased the urea-synthetic capacity as compared to that of butyrate treatment alone, possibly through the further induction of ornithine transcarbamylase expression. Therefore, the inhibition of NO production might be useful for obtaining more differentiated hepatocytes in the process of in vitro induction of hepatocyte-specific differentiation.