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.
Soler
C
C
Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Spain.
Cragoe
E J
EJ
Soley
M
M
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D006885:Hydroxybutyrates / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*
D000090:Acetoacetates; D006885:Hydroxybutyrates; D007773:Lactates; D011773:Pyruvates; D017923:Sodium-Hydrogen Exchangers; D019344:Lactic Acid; C016635:acetoacetic acid; D010042:Ouabain; D004815:Epidermal Growth Factor; D000584:Amiloride; D019289:Pyruvic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D020155:3-Hydroxybutyric Acid