Abstract

Omeprazole, a substituted benzimidazole, is known to inhibit acid secretion from parietal cells in gastric glands, and is widely utilized as a drug for peptic ulcer. To clarify the ultrastructural changes in parietal cells from long-term treatment with a therapeutic dose of omeprazole, biopsy specimens of the gastric mucosa obtained from peptic ulcer patients were morphometrically analyzed before and after omeprazole treatment. Before treatment with omeprazole, parietal cells in both the stimulated and resting stages were observed; the stimulated cells possessed smaller amounts of tubulovesicles in the cytoplasm and numerous profiles of microvilli in the intracellular canaliculi, whereas the cells in the resting phase showed numerous profiles of tubulovesicles and poorly developed microvilli in the canaliculi. Eight weeks after the onset of omeprazole treatment, the amounts of both tubulovesicles in the cytoplasm and microvilli in the intracellular canaliculi drastically decreased. These decreases in the profiles of the membrane structures with a proton pump occurred concomitantly with a significant increase in autophagic vacuole/autolysosome-like structures. These results suggest that the membrane structures with proton pump are not recycled between tubulovesicles and microvilli of intracellular canaliculi in parietal cells after omeprazole treatment, but may be sequestrated into autophagosomes and degraded by lysosomal enzymes.

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