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 gl uconeogenesis, 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 determi ne whether the mechanism by which EGF modulates any of these parameter s is dependent on the regulation of Na+/H+ exchange and/or Na+/K+-ATPa se activities. The Na+ /H+ exchange was inhibited by either amiloride or the analogue 5-(N,N-hexamethylene)amiloride (HMA), and the Na+/K+-A TPase 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 pres ence of amiloride, HMA or ouabain. The rapid EGF stimulation of glucon eogenesis was also observed in the presence of HMA or ouabain. Althoug h Na+/H+ exchange and/or Na+/K+-ATPase are regulated by EGF, our resul ts indicate that these activities are not required for the effects of EGF on gluconeogenesis and/or cytosolic and mitochondrial redox state.