LOCALIZATION OF A NOVEL PROTON PUMP INHIBITOR, LANSOPRAZOLE, IN THE GASTRIC MUCOSA OF THE RAT: A RADIOAUTOGRAPHIC STUDY

Lansoprazole (AG-1749) is a potent inhibitor of (H+K+) -ATPase and suppresses gastric acid secretion in the rat. The present study was conducted to examine the localization of lansoprazole in the gastric mucosa in the rat. Rats were given3H-labeled lansoprazole orally and sacrificed 1, 8 and 24 hr later. The distribution of the compound in the gastric mucosa was then chronologically examined by microradioautography. With light microscopy, the silver grains due to 3H were observed exclusively over the parietal cells in the gastric mucosa. Most of the grains were found over the cytoplasmic canaliculi in the parietal cells. There was no distinctive deposition of silver grains over other components such as chief cells, capillary endothelial cells or cells in lamina propria in the gastric mucosa. The number of silver grains over the parietal cells was greatest in the rat sacrificed 8 hr after administration, and was reduced 24 hr after administration. Electron microscopic observations revealed most of the silver grains localized over the microvilli of intracellular secretory canaliculi in the parietal cells. These results suggest that orally-administered lansoprazole binds to secretory membrane, possibly (H+K+) -ATPase in the parietal cells and remains there for more than 24 hr, which may explain the fact that lansoprazole shows long-lasting inhibition of gastric acid secretion in rats.