Human transforming growth factor alpha (TGF-alpha) is digested to a smaller (1-43), less biologically active, form in...

Transforming growth factor alpha (TGF-alpha) is a 50 amino acid peptide with potent proliferative and cytoprotective activity present in gastric mucosa and juice.

To determine the forms and biological activity of natural and recombinant TGF-alpha following incubation with acid pepsin.

Human gastric juice was obtained under basal conditions from patients taking acid suppressants and from volunteers undergoing intragastric neutralisation.

Samples were analysed using mass spectroscopy and/or high pressure liquid chromatography with radioimmunoassay. Biological activity was determined using thymidine incorporation into rat hepatocytes and an indomethacin/restraint induced gastric damage rat model.

TGF-alpha(1-50) is cleaved to TGF-alpha(1-43) by acid pepsin and this is the predominant form in normal gastric juice. However, intragastric neutralisation or taking acid suppressants caused the predominant form to be TGF-alpha(1-50). TGF-alpha(1-43) had only half of the ability to maximally stimulate [(3)H]thymidine incorporation into primary rat hepatocytes (28 177 (1130) DPM/well for 2.16 nM TGF-alpha(1-43) v 63 184 (3536) DPM/well for TGF-alpha(1-50); p<0.001). A similar reduced potency was seen when used in an indomethacin induced rat gastric damage model (0.18 micro mol/kg/h of TGF-alpha(1-43) reduced ulcer area by 19% whereas TGF-alpha(1-50) reduced area by 62%; p<0.001).

TGF-alpha(1-50) is cleaved to the TGF-alpha(1-43) form by acid pepsin, causing 2-5-fold loss of biological activity. Such changes may have relevance to the actions of acid suppressants and the importance of this peptide in both normal and abnormal growth.