EFFECT OF TRANSFORMING GROWTH-FACTOR-ALPHA ON GASTRIC-ACID SECRETION IN RATS AND MONKEYS

The effect of transforming growth factor-alpha was studied in histamin e-stimulated gastric acid secretion in monkeys and in pylorus-ligated rats. In monkeys, transforming growth factor-alpha given intravenously in a stepwise manner gradually reduced gastric acid secretion. A dose of 0.1 nmol/kg induced about a 50% inhibition of gastric acid output, while about 100% inhibition of the same parameter, was observed after a dose of 1 nmol/kg. Following a single administration of 1 nmol/kg i ntravenously in monkey, the maximum inhibitory effect on gastric acid output was reached 60 min after the administration of the drug, when a 91.8% inhibition was observed. Pretreatment values were reached 210-2 40 min after transforming growth factor-alpha administration. In pylor us-ligated rats, transforming growth factor-alpha, at doses of 9 and 1 8 nmol/kg produced art almost complete inhibition of gastric acid secr etion. In this model, the ED(50) was calculated to be 4.5 nmol/kg. Com parison with epidermal growth factor on the same models of gastric aci d secretion showed that these two compounds have similar inhibitory po tency. However, the effect of transforming growth factor-alpha on gast ric acid secretion in monkeys was shorter lasting than that of epiderm al growth factor.