BACKGROUND: To ascertain the mechanism for rebound acid hypersecretion after treatment with an H2-receptor blocker, we investigated the effects of ranitidine on gastric H+,K(+)-adenosine triphosphatase (ATPase) in rats. METHODS: Male Wistar rats received ranitidine (1-50 mg/kg body weight intraperitoneally twice a day for 5 days). The rats were starved for 15 h after the last treatment and then killed, and gastric vesicles containing H+,K(+)-ATPase were prepared. RESULTS: Treatment with ranitidine dose-dependently increased protein content in the gastric vesicular fraction purified from the gastric mucosa without changing total protein content. Ranitidine also increased the content of a 94,000-dalton protein, the catalytic subunit of H+,K(+)-ATPase. On the other hand, ranitidine did not affect the specific activity of the enzyme (mumol/min/mg of the gastric vesicular protein). Since gastric vesicles in the fasting state mainly consist of the tubulovesicular membrane, these results suggest that ranidine administration increases total tubulovesicular H+,K(+)-ATPase content (mumol/min/rat) by increasing the number of tubulovesicles per parietal cell. The ranitidine-induced increase in total tubulovesicular H+,K(+)-ATPase activity was still evident 1 week after treatment and returned to control level 1 month later. CONCLUSIONS: All these findings suggest that the increased content and total activity of tubulovesicular H+,K(+)-ATPase after ranitidine treatment may contribute to the mechanism for acid rebound after H2-blocker therapy.
BACKGROUND: To ascertain the mechanism for rebound acid hypersecretion after treatment with an H2-receptor blocker, we investigated the effects of ranitidine on gastric H+,K(+)-adenosine triphosphatase (ATPase) in rats. METHODS: Male Wistar rats received ranitidine (1-50 mg/kg body weight intraperitoneally twice a day for 5 days). The rats were starved for 15 h after the last treatment and then killed, and gastric vesicles containing H+,K(+)-ATPase were prepared. RESULTS: Treatment with ranitidine dose-dependently increased protein content in the gastric vesicular fraction purified from the gastric mucosa without changing total protein content. Ranitidine also increased the content of a 94,000-dalton protein, the catalytic subunit of H+,K(+)-ATPase. On the other hand, ranitidine did not affect the specific activity of the enzyme (mumol/min/mg of the gastric vesicular protein). Since gastric vesicles in the fasting state mainly consist of the tubulovesicular membrane, these results suggest that ranidine administration increases total tubulovesicular H+,K(+)-ATPase content (mumol/min/rat) by increasing the number of tubulovesicles per parietal cell. The ranitidine-induced increase in total tubulovesicular H+,K(+)-ATPase activity was still evident 1 week after treatment and returned to control level 1 month later. CONCLUSIONS: All these findings suggest that the increased content and total activity of tubulovesicular H+,K(+)-ATPase after ranitidine treatment may contribute to the mechanism for acid rebound after H2-blocker therapy.
Authors: Luisa Mota da Silva; Ligia de Moura Burci; Sandra Crestani; Priscila de Souza; Rita de Cássia Melo Vilhena de Andrade Fonseca da Silva; Nessana Dartora; Lauro Mera de Souza; Thales Ricardo Cipriani; José Eduardo da Silva-Santos; Eunice André; Maria Fernanda de Paula Werner Journal: Inflammopharmacology Date: 2017-07-28 Impact factor: 4.473