Localization of a novel proton pump inhibitor, lansoprazole, in the gastric mucosa of the rat : a radioautographic study
Localization of a novel proton pump inhibitor, lansoprazole, in the gastric mucosa of the rat : a radioautographic study
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新型质子泵抑制剂兰索拉唑在大鼠胃粘膜中的定位：放射自显影研究
DOI：
10.1267/ahc.25.405
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发表时间：
1992
影响因子：
2.4
通讯作者：
A. Shino
中科院分区：
文献类型：
--
作者：
M. Sekiguchi;H. Nagaya;H. Satoh;A. Shino
兰索拉唑（AG-1749）是一种强效（H+K+）-ATP酶抑制剂，可抑制大鼠胃酸分泌。本研究旨在检查兰索拉唑在大鼠胃粘膜中的定位。大鼠经口给予3 H标记的兰索拉唑，并在1、8和24小时后处死。然后通过显微放射自显影术按时间顺序检查化合物在胃粘膜中的分布。在光学显微镜下，观察到由于3 H导致的银颗粒仅在胃粘膜的壁细胞上。大多数颗粒位于壁细胞的胞质小管上。在胃粘膜的主细胞、毛细血管内皮细胞或固有层细胞上未见明显的银颗粒沉积。在给药后8小时处死的大鼠中，壁细胞上的银颗粒数量最多，在给药后24小时减少。电镜观察显示，大多数银颗粒位于壁细胞内分泌小管的微绒毛上。这些结果表明，兰索拉唑经口给药与分泌膜结合，可能与壁细胞中的（H+K+）-ATP酶结合，并在那里停留超过24小时，这可能解释了兰索拉唑对大鼠胃酸分泌具有持久抑制作用的事实。
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.