HEPATOCELLULAR NA+/H+ EXCHANGE IS ACTIVATED AT TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL LEVELS IN RAT BILIARY-CIRRHOSIS

Background/Aims: Rat hepatocyte Na+ H+ exchange is activated in vitro by growth factors and in vivo following partial hepatectomy. This study explored by which mechanism(s) it is activated in a cirrhosis model characterized by chronic stimulation of hepatocyte proliferation. Methods: Rat hepatocytes were isolated 4 weeks after bile duct ligation or sham operation. Intracellular pH (pHi) was fluorimetrically determined, and plasma membranes and messenger RNA (mRNA) were prepared from isolated hepatocytes by standard methods. Results: Resting pHi was higher in bile duct-ligated than in control rats (7.42 ± 0.03 vs. 7.06 ± 0.04; P < 0.001). Although plasma membrane lipid composition and intracellular buffering capacity were similar, initial Na+ H+ exchange-mediated rates of pHi recovery following acid loading were higher in bile duct-ligated than in control rats (0.098 ± 0.011 vs. 0.055 ± 0.005 pH units/min; P < 0.05). The antiporter's set point was shifted 0&#x0303;.3 pH units towards more alkaline values and its steady-state mRNA levels were doubled after bile duct ligation. Conclusions: Hepatocellular Na+ H+ exchange is transcriptionally and posttranscriptionally activated in rat biliary cirrhosis further supporting a relationship between hepatocyte proliferation and Na+ H+ exchange activation. © 1994.