EPIDERMAL GROWTH-FACTOR IS DIGESTED TO SMALLER, LESS ACTIVE FORMS IN ACIDIC GASTRIC-JUICE

Background/Aims: Epidermal growth factor (EGF) is present in gastric j uice and has potent mitogenic properties. The stability of EGF in gast ric juice under various physiological and pathophysiological condition s was examined. Methods: Recombinant human EGF(1-53) was incubated wit h HCl containing pepsin. We also determined the forms of EGF present i n the gastric juice of patients under basal conditions, patients takin g the acid suppressant omeprazole, patients with achlorhydria, and vol unteers undergoing intragastric neutralization with NaHCO3 (n = 6 per group). Samples were analyzed using mass spectroscopy and/or high-pres sure liquid chromatography followed by radioimmunoassay. The effect of acid and pepsin digestion on EGF bioactivity was determined using an in vitro hepatocyte bioassay and an in vivo cytoprotection assay in th e rat stomach. Results: EGF(1-53) was digested to the EGF(1-49) and EG F(1-46) forms in all samples containing pepsin when the pH was <4. In gastric juice samples with pH >4, the proportion of intact EGF increas ed to about 60%. For both methods of bioassay, intact EGF(1-53) was ab out 3-4 times as potent as acid and pepsin-treated EGF. Conclusions: E GF is produced in the 1-53 form but is rapidly cleaved to smaller, les s active forms in acidic gastric juice. In contrast, only a small prop ortion of the EGF is cleaved if the pH is maintained above 4. This mec hanism may be relevant to the healing process of acid suppressants.