Annexin 7 in the Regulation of Gastric Acid Secretion

Abstract

Background/Aims: Glucocorticoids enhance gastric acid secretion and inhibit gastric cyclooxygenase, thus downregulating formation of PGE₂, an inhibitor of gastric acid secretion. In erythrocytes, PGE₂ formation is inhibited by annexin 7. The present study thus explored whether annexin 7 participates in the regulation of gastric acid secretion. Methods: Annexin 7 protein expression was determined by Western blotting, cytosolic pH (pHi) of parietal cells utilizing BCECF-fluorescence, and gastric acid secretion by determination of Na⁺-independent pHi recovery from an ammonium pulse (∆pHi/min). Experiments were performed in isolated glands from gene targeted mice lacking annexin 7 (anx7^-/-) and in respective wild type animals (anx7^+/+). Results: Prior to treatment pHi and ∆pHi/min were similar in isolated gastric glands from anx7^-/- and from anx7^+/+ mice. Aspirin (100 µM added to the glands 1 hr prior to the experiment) significantly increased ∆pHi/min to similar values in both genotypes. The administration of dexamethasone (10 µg/g BW subcutaneously for 4 consecutive days prior to the experiments) significantly increased ∆pH/min in anx7^+/+ mice but not in anx7^-/- mice. Following dexamethasone treatment, the luminal pH was significantly lower and the acid content significantly higher in anx7^+/+ mice than in anx7^-/- mice. An increase of extracellular K⁺ concentration to 35 mM (replacing Na⁺/NMDG⁺) significantly increased ∆pHi/min in both genotypes. In neither genotype dexamethasone increased ∆pH/min further in the presence of 35 mM K⁺ or presence of aspirin. Conclusions: Annexin 7 is required for the stimulation of gastric acid secretion by glucocorticoids.