Changes in subcellular structures of parietal cells in the rat gastric gland after omeprazole.
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.
Furuhashi
M
M
Department of Gastroenterology, Universitp6of Tsukuba, Japan.
Nakahara
A
A
Fukutomi
H
H
Kominami
E
E
Uchiyama
Y
Y
D000818:Animals; D002401:Cathepsin B / Q000032:analysis; D002462:Cell Membrane / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000648:ultrastructure; D005755:Gastrins / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D008871:Microvilli / Q000187:drug effects; D009853:Omeprazole / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains
D005755:Gastrins; D002401:Cathepsin B; D009853:Omeprazole