Ultrastructure of enterochromaffin-like cells in rat stomach: effects of alpha-fluoromethylhistidine-evoked histamine depletion and hypergastrinemia.
Histamine-producing enterochromaffin-like (ECL) cells are numerous in the oxyntic mucosa of the rat stomach. They respond to gastrin by secretory activation, hypertrophy and hyperplasia. They contain cytoplasmic granules (median profile diameter 120 nm), secretory vesicles (180 nm) and microvesicles (70 nm). alpha-Fluoromethylhistidine (alpha-FMH) depletes histamine from the ECL cells by inhibiting the histamine-forming enzyme histidine decarboxylase. Long-term hypergastrinemia, evoked by omeprazole, increases the ECL-cell histamine concentration. The way in which chronic histamine depletion affects omeprazole-induced ECL-cell hypertrophy, and the ways in which granules and vesicles in the ECL cells respond to alpha-FMH and/or omeprazole have been studied. Rats were treated with alpha-FMH (3 mg/kg per h subcutaneously), omeprazole (400 micromol/kg per day orally), alpha-FMH+omeprazole, or vehicle for 6 weeks. ECL cell profiles in electron micrographs were analysed panimetrically. The results show that the omeprazole-evoked hypertrophy of the ECL cells is not affected by depletion of ECL-cell histamine, thereby supporting the view that ECL-cell histamine is not important for full expression of the gastrin-evoked trophic effects on the ECL cells. The loss of ECL-cell histamine following treatment with alpha-FMH and with alpha-FMH+omeprazole is associated with a greatly reduced size of the secretory vesicle compartment. The granules, on the other hand, are unaffected by alpha-FMH and alpha-FMH+omeprazole. Omeprazole treatment leads to the appearance of numerous vacuoles (with profile diameter greater than 500 nm); such vacuoles are not observed in the ECL cells of rats treated with alpha-FMH or alpha-FMH+omeprazole. The omeprazole-induced increase in ECL-cell histamine is associated with an increase in the compartment composed of secretory vesicles and vacuoles. The findings support the hypothesis that secretory vesicles (and vacuoles) represent a major storage site of ECL-cell histamine.
Chen
D
D
Department of Pharmacology, University of Lund, Sölvegatan 10, S-22362 Lund, Sweden.
Zhao
C M
CM
Andersson
K
K
Sundler
F
F
Håkanson
R
R
D000818:Animals; D048429:Cell Size / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects; D004759:Enterochromaffin Cells / Q000648:ultrastructure*; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology*; D005755:Gastrins / Q000097:blood*; D006636:Histamine Release / Q000187:drug effects; D008762:Methylhistidines / Q000494:pharmacology*; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014617:Vacuoles / Q000187:drug effects
D005755:Gastrins; D008762:Methylhistidines; C028309:alpha-fluoromethylhistidine; D009853:Omeprazole