EFFECT OF H-EGF AND H-EGF 1-48 ON HISTAMINE-STIMULATED GASTRIC-ACID SECRETION IN RATS AND MONKEYS

The effect of human epidermal growth factor (h-EGF) and its derivative human epidermal growth factor 1-48 (h-EGF 1-48) on histamine-stimulat ed gastric acid secretion was studied in monkeys and rats. In monkeys, both h-EGF and h-EGF 1-48 given intravenously (iv) in a stepwise mann er and in doses ranging from 0.01 to 10 nmol/kg, gradually suppressed gastric acid secretion. At the highest dose tested. both compounds ess entially abolished gastric acid output. In the same animals, iv admini stration of 1 nmol/kg of h-EGF or h-EGF 1-48 caused an inhibition of g astric acid output that reached a peak at 90 and 60 min after the admi nistration of h-EGF or h-EGF 1-48 respectively. After this maximum gas tric inhibitory effect, a gradual return toward pre-injection values w as observed. In rats. after subcutanous (sc) administration, both h-EG F and h-EGF 1-48 dose-dependently inhibited histamine-stimulated gastr ic acid output as measured 60 min after the administration of the comp ounds. The maximum inhibitory activity on gastric acid output. observe d at a dose of 100 nmol/kg. was 74.4% and 76.0% for h-EGF and h-EGF 1- 48 respectively. The same dose of both compounds. however, failed to s ignificantly inhibit gastric acid secretion when administered orally. In all the studies h-EGF 1-48 showed activity and potency comparable t o h-EGF. In addition to the demonstration of gastric secretion inhibit ory activity of h-EGF in primates. this study indicates that h-EGF 1-4 8 has an inhibitory activity on the secretory parameters studied which is indistinguishable from the activity of h-EGF.