Reversibility of omeprazole-evoked changes in the ultrastructure of ECL cells in the rat stomach.
The ECL cells are histamine- and peptide hormone-producing endocrine cells in the rat oxyntic mucosa. They are rich in secretory vesicles and also contain microvesicles and electron-dense granules. They operate under the control of circulating gastrin. In the present study, we examined the ECL-cell ultrastructure after long term treatment with omeprazole, which is known to induce hypergastrinemia, and after withdrawal of the drug. Rats received omeprazole (400 micromol/kg per day, orally) for 16 days and were killed 1, 5, 20, or 40 days after the last dose of the drug. Oxyntic mucosal specimens were processed for electron microscopy. Electron micrographs of ECL-cell profiles were analyzed planimetrically. The ECL-cell profile area increased promptly in response to omeprazole, the secretory vesicles and granules were reduced in number and volume density, the microvesicles were unchanged in number but reduced in volume density, and vacuoles appeared. Within a week after stopping the omeprazole treatment, the numbers and volume densities of secretory vesicles and microvesicles returned to pre-stimulation values. Also, the vacuoles disappeared promptly. The ECL-cell profile area decreased below the pre-stimulation level within five days after stopping treatment, while, in contrast, the granules increased in number and volume density. Somewhat surprisingly, the cell size and the granule compartment did not return to normal until 40 days after stopping treatment.
Zhao
C
C
Department of Pharmacology, University of Lund, Sölvegatan 10, S-223 62 LUND, Sweden.
Chen
D
D
Kimura
K
K
Hâkanson
R
R
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000648:ultrastructure*; D006056:Golgi Apparatus / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009853:Omeprazole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000166:cytology*
D000897:Anti-Ulcer Agents; D009853:Omeprazole