Effects of epidermal growth factor on gluconeogenesis and cellular redox state do not require Na+/H+ exchange or Na+/K(+)-ATPase activities.

Epidermal growth factor (EGF) triggers rapid and delayed effects on gluconeogenesis, cytosolic (lactate/pyruvate ratio) and mitochondrial (3-hydroxybutyrate/acetoacetate ratio) redox states (Soler, C. and Soley, M., Biochem. J., 294 (1993) 865-872). This study attempts to determine whether the mechanism by which EGF modulates any of these parameters is dependent on the regulation of Na+/H+ exchange and/or Na+/K(+)-ATPase activities. The Na+/H+ exchange was inhibited by either amiloride or the analogue 5-(N,N-hexamethylene)amiloride (HMA), and the Na+/K(+)-ATPase activity was inhibited by ouabain. The delayed EGF inhibition of gluconeogenesis, increase of the lactate/pyruvate ratio and decrease in the 3-hydroxybutyrate/acetoacetate ratio were unaltered in the presence of amiloride, HMA or ouabain. The rapid EGF stimulation of gluconeogenesis was also observed in the presence of HMA or ouabain. Although Na+/H+ exchange and/or Na+/K(+)-ATPase are regulated by EGF, our results indicate that these activities are not required for the effects of EGF on gluconeogenesis and/or cytosolic and mitochondrial redox state.