Secretory organelles in ECL cells: effects of pharmacological blockade of the gastrin/CCK2 receptor versus its elimination by gene targeting.
Histamine-producing ECL cells are numerous in the stomach. They express gastrin/CCK2 receptors and respond to gastrin by releasing histamine. Ultrastructurally, they display numerous and very characteristic secretory organelles: granules, secretory vesicles and microvesicles. This paper focuses on the impact of the gastrin/CCK2 receptor on the ultrastructure of the ECL cells. The effects of pharmacological blockade of the receptor are compared with the effects of receptor elimination following selective gene targeting. Long-term administration of powerful gastrin/CCK2 receptor antagonists was found to induce hypotrophy of rat stomach ECL cells with reduced number of granules, secretory vesicles and microvesicles. In gastrin/CCK2 receptor knockout mice ECL cells, i.e., histamine-storing cells with the characteristic ultrastructure of ECL cells, had disappeared from the oxyntic mucosa and been replaced by a novel population of endocrine-like cells. These cells harbored granules and microvesicles, but were devoid of histamine and secretory vesicles. We suggest that the gastrin/CCK2 receptor is important for the proper differentiation of the ECL cells and for maintaining their characteristic ultrastructure.
Zhao
Chun-Mei
CM
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Chun-Mei.Zhao@ntnu.no
Håkanson
Rolf
R
Chen
Duan
D
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D019861:Enterochromaffin-like Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D015388:Organelles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010671:Phenylurea Compounds / Q000494:pharmacology; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; D001569:Benzodiazepines; C087260:YM 022; C104428:YF 476