Pediatr. Res. 15: 921-925 (1981) corticosteroids gastric acid development stomach fetus The pH of gastric fluid was measured in rat fetuses during the ANIMALS last 3 days of gestation. On day 19, the gastric pH was close to neutral. During the night of day 20, the pH was clearly lowered Sherman rats, fed a coinmercial diet (U.A.R., France), were (6.11 k 0.15 units), this decrease becoming more marked on the used for this study. To obtain fetuses of known age, females were following day. At birth (day 22), just before the first feeding, the mated overnight. Gestation was detected by palpation 2 wk later; pH of gastric fluid reached the mean value of 2.98 k 0.14 units. the day after the night of mating was considered as day zero of This drop in gastric pH was concomitant with an increase in gestation. In this strain, delivery occurs in the night of day 21. chloride concentration whereas the gastric Pcoz remained constant. These results imply that in term rat fetuses, the gastric CHEMICAL rnucosa secretes fixed acid, very likely hydrochloride acid. Ontogenesis of Gastric Acid Secretion in Fetal RatBERNARDThe administration of acetazolamide (inhibitor of carbonic anhydrase) to 20-day-old fetuses did not suppress the spontaneous acidification of gastric fluid, although the enzyme activity was reduced by approximately 80%. Moreover, the gastric pH in acetazolamide-injected fetuses was markedly lower than in the noninjected littermates. The administration of NaCl solution (acetazolamide vehicle) had no effect on the carbonic anhydrase activity but clearly decreased the pH of gastric fluid. Thus, the drop of gastric pH produced by injection of acetazolamide or saline solution alone probably results from a stress effect of puncture.In fetuses from adrenalectomized, metopirone-treated mothers, the injection of NaCl solution no longer had effect on the pH of gastric fluid whereas triamcinolone injection produced a clear decrease in the gastric pH 3 hr later. SpeculationCorticosteroids could play an important role in the development of H+ generation processes in parietal cells during the fetal period of life.Electron microscopic studies have shown that in some mammals species, including man, parietal cells of the gastric mucosa begin to develop during intrauterine life (14,15,25). It has been observed that gastric acid secretion takes place before birth in guinea pig (28), lamb (16), and rabbit (30). Newborn human infants have an intragastric pH ranging from 5.5 to 7; this pH then strongly decreases by 4 to 5 hr of age (1, 13). As far as we know, there is Acetazolamide was purchased from Theraplix (Paris, France), and triamcinolone was purchased from Sigma Chemical Co. (Saint Louis, MO). Metopirone was a gift of the Ciba laboratory, (Basel, Switzerland). EXPERIMENTAL PROCEDURESPregnant rats were adrenalectomized under ether anaesthesia on day 16 of gestation and then received 10 mg metopirone by intraperitoneal injections twice a day until the time of sacrifice. Such treatment suppresses, or at least strongly reduces, th...

Gastric H+-K+-ATPase activity was examined in subcellular fractions (P1, 1,000 g; P2, 20,000 g; P3, 100,000 g) obtained from fundic mucosae of fetal, newborn, and adult rats. Depending on the tissue secretory state the distribution of this enzyme activity predominates in P3, i.e., resting adult, or in P2, i.e., stimulated adult, while total enzyme activity (P2 + P3) remains constant. Enzyme activity was detected as soon as day 19 of gestation and P2 + P3 reached 2.2 +/- 0.2 mumol Pi X mg prot-1 X h-1 at parturition. H+-K+-ATPase activity steadily decreased from 4.0 +/- 0.7 mumol Pi X mg prot-1 X h-1 on day 6 after birth to approximately 0 on day 12. This activity recovered as soon as day 13 (3.5 +/- 0.6 mumol Pi X mg prot-1 X h-1) and continued to rise slowly until adulthood. Incubation of subcellular fractions with 0.1 mM omeprazole resulted in a total loss of H+-K+-ATPase activity at all the stages of development examined. These studies of functional relationship during the development between gastric acid secretion and distribution of gastric H+-K+-ATPase activity among P2 and P3 fractions indicate that this last could be considered as an index of the secretory state of the parietal cell. This enzyme's pattern of development in P2 + P3, correlated with the one previously observed for stimulated H+ secretion in intact tissue, suggest that the H+-K+-ATPase is the limiting step in response to secretagogues during postnatal period.

Rat stomach sensitivity to pentagastrin was examined in fetal (days 19--21) and newborn (5--day-old) preparations in vivo and in vitro. Gastric acidification in vivo was expressed as the gastric content pH and in vitro as the net transepithelial H+ fluxes determined in an Ussing chamber. In both preparations, fetal stomach first responded to pentagastrin on day 20. Dose-dependent H+ secretion was demonstrated in vitro for pentagastrin concentrations of 10(-8) to 10(-6) M, with half-maximal stimulations at 1.9 x 10(-7) and 4 x 10(-7) M on days 20 and 21, respectively. In contrast, isolated fundic mucosa of 5-day-old rat pups exhibited very low H+ secretion rates, and pentagastrin did not significantly stimulate acid output. Fetal serum immunoreactive gastrin was detected as early as day 16 in fairly constant concentrations (about 77.5 pg eq synthetic human gastrin/ml). These results indicate that, although immunoreactive gastrin is present in serum as early as day 165, pentagastrin does nt stimulate acid secretion until day 20 when fetal stomach exhibits active H+ secretion and decreased passive permeability. Pentagastrin sensitivity disappears during the 1st days of extrauterine life. These findings strongly suggest that the development of pentagastrin sensitivity in rat stomach is biphasic.

In vivo fetal rat stomach produces HCl 48 h before birth. This study examines the mechanisms of H+ secretion from days 19 to 21 before birth. Isolated fetal stomachs were mounted as flat sheets in Ussing chambers for measurement of the transepithelial H+ fluxes (JH+) and short-circuit current (Isc), as indexes of the active ionic fluxes, and for measurement of total ionic conductance (G) and unidirectional mannitol fluxes from serosa to mucosa (JMans leads to m), as indexes of passive permeability. The results indicate that JH+ was absent at day 19 but reached 0.75 +/- 0.1 and 0.75 +/- 0.09 mueq . h-1 . cm-2 at days 20 and 21, respectively. Concomitantly, Isc increased significantly (56%) between days 19 and 20 in the direction of anion secretion or cation absorption. Parallel reductions in G (45%) and in JMans leads to m (66%) were observed between days 19 and 20. In conclusion, the simultaneous appearance of active H+ secretion and decreased passive transepithelial permeability strongly suggests that both processes are involved in the mechanism of acidification of the fetal rat stomach before birth.

A bovine milk diet (BM) resulted in remarkable changes in histamine H2 receptor activity (sensitization) and PGE2 receptor activity (desensitization) in gastric glands isolated from adult rats. In contrast, the receptor-cAMP systems sensitive to glucagon(s) and secretin in parietal cells and muco-peptic cells were unaffected. In the two experimental groups, cimetidine produced a parallel displacement of the histamine dose-response curve suggesting competitive inhibition between this classical H2 receptor antagonist and histamine. The BM diet reduced the histidine decarboxylase activity in rat gastric mucosa; the histamine content was not significantly different in control and BM-fed rats. There was no alteration of the circadian rhythm of the parietal cell (ultrastructural changes: microvilli, tubulo-vesicles) determined at intervals of 6 hours in milk-fed rats. Prostaglandins and other components in milk (EGF, somatostatin, etc.) might therefore protect gastric mucosa by a differential control of PGE2 and histamine H2 receptor activity, either directly (PGE2 and EGF in milk) or indirectly (inhibition of endogeneous histamine synthesis/release and stimulation of prostaglandin synthesis/release).