Effect of transforming growth factor-α on gastric acid secretion in rats and monkeys

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Abstract
The effect of transforming growth factor-α was studied in histamine-stimulated gastric acid secretion in monkeys and in pylorus-ligated rats. In monkeys, transforming growth factor-α 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 intravenously 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 210–240 min after transforming growth factor-α administration. In pylorus-ligated rats, transforming growth factor-α, at doses of 9 and 18 nmol/kg produced an almost complete inhibition of gastric acid secretion. In this model, the ED50 was calculated to be 4.5 nmol/kg. Comparison with epidermal growth factor on the same models of gastric acid secretion showed that these two compounds have similar inhibitory potency. However, the effect of transforming growth factor-α on gastric acid secretion in monkeys was shorter lasting than that of epidermal growth factor.