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Changes in subcellular structures of parietal cells in the rat gastric gland after omeprazole
M Furuhashi1, A Nakahara, H Fukutomi
1Department of Gastroenterology, Universitp6of Tsukuba, Japan.
Abstract:
Omeprazole, an inhibitor of gastric acid secretion, was administered to rats at a dosage of 20 mg/kg/day for 14 and 35 days, and subsequent changes in subcellular structures of parietal cells were analyzed using morphometry and immunocytochemistry. Plasma gastrin levels were also examined, showing two times higher levels in the experimental groups than in the non-treated control. The volume and surface densities significantly decreased in tubulovesicles of the cells in the experimental rats. In the long term treatment of omeprazole (35 days), the volume density of microvilli on the membranes of secretory canaliculi in the cells also decreased significantly, whereas that of lysosomes clearly increased. By electron microscopy, many dense bodies of various shapes often appeared in the cytoplasm of parietal cells after the omeprazole treatment. Immunocytochemistry revealed that large granular immunodeposits for cathepsin B increase in the epithelial cells of the gastric glands after omeprazole treatment. These results suggest that omeprazole induces quantitatively significant decreases in both tubulovesicles and canalicular microvilli. The decreases in these membrane structures may possibly be ascribed to the degradation of the membrane in lysosomes; the proton pump on the membranes bound irreversibly with omeprazole is believed destined to be degraded in lysosomes.
Insights
Omeprazole treatment in rats significantly reduced parietal cell tubulovesicles and microvilli. This suggests omeprazole may lead to lysosomal degradation of these membrane structures, including the proton pump.
Area of Science:
- Cell Biology
- Gastroenterology
- Pharmacology
Background:
- Omeprazole is a widely used proton pump inhibitor for treating acid-related disorders.
- Its long-term effects on the cellular ultrastructure of gastric parietal cells require further investigation.
Purpose of the Study:
- To investigate the subcellular structural changes in rat gastric parietal cells following omeprazole administration.
- To examine the impact of omeprazole on plasma gastrin levels and lysosomal activity.
Main Methods:
- Rats were treated with omeprazole (20 mg/kg/day) for 14 and 35 days.
- Morphometry, immunocytochemistry, and electron microscopy were employed to analyze parietal cell structures.
- Plasma gastrin levels were measured.
Main Results:
- Omeprazole treatment led to a significant decrease in tubulovesicles and microvilli in parietal cells.
- Long-term treatment (35 days) showed increased lysosome volume density and appearance of dense bodies.
- Plasma gastrin levels doubled in treated rats, and cathepsin B immunodeposits increased.
Conclusions:
- Omeprazole induces significant quantitative reductions in parietal cell tubulovesicles and microvilli.
- These structural changes may result from lysosomal degradation, potentially targeting omeprazole-bound proton pumps.
- The findings provide cellular insights into the mechanism of action and potential long-term effects of omeprazole.