EGF MODULATION OF NA+ H+ ANTIPORT IN RAT HEPATOCYTES - DIFFERENT SENSITIVITY IN ADULT AND FETAL CELLS/

The modulation by epidermal growth factor (EGF) of the Na+/H+ antiport in fetal and adult rat hepatocytes was studied in nominally HCO3--fre e solution. EGF (10 nM) activated the antiport in adult rat hepatocyte s by 0.22 +/- 0.03 (mean +/- SD; n = 10) pH units over basal value, me asured with the fluorescent pH-sensitive intracellular probe, 2',7'-bi s(carboxyethyl)-5(6)carboxyfluorescein (BCECF). The effect of EGF was inhibited by amiloride analogue 5-(N-ethyl-N-isopropyl)amiloride (EIPA ), by ouabain, inhibitor of the Na+ pump, and by erbstatin analogue, a n inhibitor of the tyrosine kinase activity of the EGF receptor. The e ffect of EGF on Na+/H+ antiport in adult rat hepatocytes appeared to b e mediated by both protein kinase C (PKC) and G protein system. No eff ect of EGF and phorbol 12-myristate 13-acetate, an activator of PKC, o n the Na+/H+ antiport was observed in fetal hepatocytes of 20 and 22 d ays. A different sensitivity of the antiport to high concentrations of amiloride and EIPA suggests that altered amount of tha Na+/H+ antipor t units or different isoforms could be expressed in fetal compared wit h adult cells.