TURNOVER OF THE GASTRIC H+,K+-ADENOSINE TRIPHOSPHATASE ALPHA-SUBUNIT AND ITS EFFECT ON INHIBITION OF RAT GASTRIC-ACID SECRETION

Background & Aims: The rate of turnover and the effect of inhibition of acid secretion on the turnover of gastric H+,K+-adenosine triphosphatase (ATPase) is unknown. The aim of this study was to determine the turnover of the a subunit of gastric H+,K+-ATPase in rats under control conditions and during inhibition of acid secretion by ranitidine or omeprazole. Methods: The turnover of the cr subunit of the ATPase was determined by measuring the loss of incorporated S-35-methionine. This was compared with the rate of recovery of K+-stimulated ATPase activity in the omeprazole-treated animals. Results: The half-life of the or subunit was 54 hours. A 1-week treatment with omeprazole had no significant effect, but the half-life increased to 125 hours (P < 0.01) after continuous ranitidine infusion. After omeprazole treatment, K+-stimulated ATPase activity recovered with a half-time of 15 hours. Conclusions: The turnover of the gastric ATPase subunit was independent of omeprazole inhibition but was prolonged by ranitidine. The effect of ranitidine suggests that the resting pump in tubulovesicles may turn over more slowly than the stimulated pump in the secretory canaliculus. The rapid recovery of ATPase activity compared with turnover after omeprazole is caused by both H+,K+-ATPase synthesis and loss of covalently bound drug.