ONTOGENIC DIFFERENCES IN THE INHIBITION OF GASTRIC-ACID SECRETION BY EPIDERMAL GROWTH-FACTOR

Gastric secretions were studied in rats by pyloric ligation in vivo. T he effects of epidermal growth factor (EGF) administered s.c. on gastr ic secretion were evaluated at different stages of development (8, 14, 20 and 30 postnatal days). The rates of fluid, protein and acid outpu ts were very low in developing rats but increased in maturing rats. Th e rate of acid output in 8- day-old rats (3.83 +/- 1.16) was not diffe rent from that in 14-day-old rats (4.84 +/- 0.99), whereas the rate of acid output in 20-day-old rats was 11 -fold greater than that in 1 4- day-old rats, and it was 21-fold greater in 30-day-old rats. Subcutane ous administration of 30 mug/kg b.wt. of EGF significantly suppressed the gastric secretion of fluid, protein and acid in 20- and 30-day- ol d rats. In 30-day-old rats, acid output was 85% lower at 1 hr after EG F administration and in 20-day-old rats it was 85% lower at 2 hr and 5 0% lower at 3 hr. Interestingly, EGF had no effect on basal gastric se cretions in 8- and 14-day-old rats; EGF also had no effect on the gast ric acid output that was stimulated by pentagastrin administration in 14-day-old rats. In 20-day-old rats, inhibitory effects of EGF lasted for 3 hr before gastric secretions rebounded to normal levels, but inh ibition lasted for only 1 hr in 30-day-old rats. EGF was nearly 15-fol d more potent in 20-day-old rats than in 30-day-old rats; the A50 (95% C.L.) values for EGF in 20- and 30-day-old rats were 7.5 (4.6-12.4) a nd 117.3 (77.2-168.5) mug/kg b.wt., respectively. EGF up to 950 mug/kg b.wt. showed no effect in 8- and 14-day-old rats. EGF receptors in ga stric mucosal membranes, as analyzed by radioligand binding showed no age-related differences in their K(d) values, whereas maximum binding values in membranes prepared from 20-day-old rats was significantly gr eater than those in membranes prepared from 8-, 14- or 30-day-old rats . These results demonstrate ontogenic differences in the potency and e fficacy of EGF in inhibiting gastric secretions in rats.