MECHANISMS OF GASTRIC-ACID SECRETION IN THE FETAL RABBIT

Background. The parietal cell specific protein H+/K+-adenosine triphos phatase (H+/K+-ATPase) is responsible for gastric acid secretion in ad ult mammals; however, its ontogeny and role in fetal acid secretion ar e unknown. The purpose of this study was twofold: (1) to determine the ontogeny of gastric acid secretion and parietal cell H+/K+ ATPase exp ression in the fetal rabbit and (2) to determine the rob of H+/K+-ATPa se in fetal acid secretion. Methods, For the ontogeny studies 88 fetus es from nine time-mated rabbits were studied at successive gestational ages. Gastric fluid and amniotic fluid pH were measured, and total ga stric 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 determi ne 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 ne utral (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 b y day 30. By use of Western blot analysis and immunohistochemistry, ga stric microsomal H+K+-ATPase expression was absent from days 20 throug h 25 of gestation and first detectable at day 26, with qualitative inc reases to term. Omeprazole significantly inhibited pH (5.45 +/- 0.13 i n 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 increase s to term, (2) gastric microsomal H+/K+-ATPase expression is first det ectable at day 26 of gestation and (3) omeprazole inhibits, but does n ot abolish, gastric acid secretion in the fetal rabbit. We conclude th at gastric acid secretion is present before birth in the fetal rabbit and is mediated, in part, by omeprazole-sensitive H+/K+-ATPase.