MECHANISMS OF GASTRIC-ACID SECRETION IN THE FETAL RABBIT

Background. The parietal cell specific protein H+/K+-adenosine triphosphatase (H+/K+-ATPase) is responsible for gastric acid secretion in adult mammals; however, its ontogeny and role in fetal acid secretion are unknown. The purpose of this study was twofold: (1) to determine the ontogeny of gastric acid secretion and parietal cell H+/K+ ATPase expression in the fetal rabbit and (2) to determine the rob of H+/K+-ATPase in fetal acid secretion. Methods, For the ontogeny studies 88 fetuses from nine time-mated rabbits were studied at successive gestational ages. Gastric fluid and amniotic fluid pH were measured, and total gastric acid was determined by titration. Gastric microsomal protein was analyzed by Western blot analysis for H+K+-ATPase expression by wing a monoclonal antibody to the 94 kd alpha-catalytic subunit. To determine the role of H+/K+-ATPase in fetal acid secretion, 37 fetuses at day 26 from four time-mated rabbits were treated with (1) omeprazole (20 mg/g injection into the amniotic sac (n = 13), (2) carrier injection (n = 12), or 3) no injection (n = 12). Fetal gastric pH and titratable acid were measured at day 28. Results, Amniotic fluid pH was neutral (7.44 to 7. 64) throughout the third trimester. Gastric fluid pH was neutral (7.42 to %51) until day 25, when it decreased to 7.16 +/- 0.23 (p < 0.05) and subsequently fell to 5.37 +/- 0.05 by day 30 Titratable gastric acid (micromoles) increased from 0 at day 20 to 54.7 +/- 5.4 by day 30. By use of Western blot analysis and immunohistochemistry, gastric microsomal H+K+-ATPase expression was absent from days 20 through 25 of gestation and first detectable at day 26, with qualitative increases to term. Omeprazole significantly inhibited pH (5.45 +/- 0.13 in controls, 5.56 +/- 0.12 with carrier injection, and 6.01 + 0.01 with omeprazole injection; p < 0.05). Conclusions, These data suggest that (1) gastric acid secretion begins at day 25 of gestation and increases to term, (2) gastric microsomal H+/K+-ATPase expression is first detectable at day 26 of gestation and (3) omeprazole inhibits, but does not abolish, gastric acid secretion in the fetal rabbit. We conclude that gastric acid secretion is present before birth in the fetal rabbit and is mediated, in part, by omeprazole-sensitive H+/K+-ATPase.