Epidermal Growth Factor Up-Regulates Intestinal Na⁺/H⁺ Exchange Activity

The present studies were designed to examine the regulation of Na⁺/H⁺ exchange activity by epidermal growth factor (EGF) in an in vitro system. Na⁺/H⁺ exchange activity was determined in brush-border membranes isolated from rat jejunal enterocytes incubated with epidermal growth factor and a number of second messengers. EGF at physiological concentrations stimulated Na⁺/H⁺ exchange activity without affecting vesicle size. The stimulation of Na⁺/H⁺ activity was the result of increasing V_max of Na⁺/H⁺ (6.0 ± 0.4 compared with 3.3 ± 0.27 nmol/mg protein/5 sec, P < 0.01). K_m values of the Na⁺/H⁺ exchanger in brush-border membrane from cells stimulated with EGF and controls were similar (16.0 ± 3.0 vs 13.0 ± 3.0, respectively). Na⁺/H⁺ activity was inhibited by phorbol esters, calmodulin, and cyclic AMP. The effects of EGF, calmodulin, cyclic AMP, and phorbol esters were dependent on ATP, because depleting the cells from ATP masked the effects on Na⁺/H⁺ exchange activity. The results suggest that EGF stimulates Na⁺/H⁺ exchange activity in the enterocytes. This stimulation is most likely not via activation of the phosphatidylinositol pathway.