EFFECTS OF RANITIDINE ON GASTRIC VESICLES CONTAINING H-ADENOSINE TRIPHOSPHATASE IN RATS(,K+)

Background: To ascertain the mechanism for rebound acid hypersecretion after treatment with an H-2-receptor blocker, we investigated the eff ects of ranitidine on gastric H+,K+-adenosine triphosphatase (ATPase) in rats. Methods: Male Wistar rats received ranitidine (1-50 mg/kg bod y weight intraperitoneally twice a day for 5 days). The rats were star ved for 15 h after the last treatment and then killed, and gastric ves icles containing H+,K+-ATPase were prepared. Results: Treatment with r anitidine dose-dependently increased protein content in the gastric ve sicular fraction purified from the gastric mucosa without changing tot al protein content. Ranitidine also increased the content of a 94,000- dalton protein, the catalytic subunit of H+,K+-ATPase. On the other ha nd, ranitidine did not affect the specific activity of the enzyme (mu mol/min/mg of the gastric vesicular protein). Since gastric vesicles i n the fasting state mainly consist of the tubulovesicular membrane, th ese results suggest that ranitidine administration increases total tub ulovesicular H+,K+-ATPase content (mu mol/min/rat) by increasing the n umber of tubulovesicles per parietal cell. The ranitidine-induced incr ease in total tubulovesicular H+,K+-ATPase activity was still evident 1 week after treatment and returned to control level 1 month later. Co nclusions: All these findings suggest that the increased content and t otal activity of tubulovesicular H+,K+-ATPase after ranitidine treatme nt may contribute to the mechanism for acid rebound after H-2-blocker therapy.