During our studies on the active moiety of anti-ulcerogenic protein in rabbit skin tissues infected with vaccinia virus, we obtained a tetrapeptide, Gly-Ser-His-Lys (GSHL), as the smallest essential residue. The action of this peptide widely covered against various experimental ulcers in rats induced by pylorus-ligation, restraint plus water immersionstress (minimum effective dose, mg/kg, i. v. ; 5.0), aspirin (5.0), histamine (5.0), cortisone (2.5/d), cysteamine (10) and acetic acid (1.0/d). In the respect of minimum effective dose, the effect of GSHL was 5-20 fold stronger than that of cimetidine, except for acetic acidinduced ulcers. Histological finding of acetic acid-induced ulcers revealed that GSHL treatment shortened an apparent defect of mucosa, a true defect of mucosa and rupture of muscaliris mucosae, and that it increased healing index and mucosal regeneration index. The peptide significantly decreased serum gastrin level, increased mucosal and stromal hexosamine contents and also increased mucosal blood flow in stress-treated rats. It significantly inhibited gastric secretion in pylorus-ligated rats. The mechanism of the action of GSHL appears to be due to the restorative effect against defected mucosa and anti-secretory effect.
