Functionally impaired, hypertrophic ECL cells accumulate vacuoles and lipofuscin bodies. An ultrastructural study of ECL cells isolated from hypergastrinemic rats.
ECL cells in the oxyntic mucosa of stomach control gastric acid secretion by mobilizing histamine in response to gastrin. They respond to gastrin also with hypertrophy and hyperplasia. ECL cells exhibit functional impairment upon long-term gastrin stimulation. The impairment is manifested in a gradual decline of the activity of the histamine-forming enzyme per individual ECL cell and in a failure of gastrin to mobilize histamine. The mechanism behind this impairment is unknown. In the present study, rats were treated with the proton pump inhibitor pantoprazole for 45 days to induce sustained hypergastrinemia. The ECL cells were isolated from normogastrinemic and hypergastrinemic rats and size-separated from other mucosal cells by the elutriation technique. The total ECL cell number was twofold higher in hypergastrinemic rats than in normogastrinemic rats, and most of the cells appeared in elutriation fractions where large cells predominate. The ECL cells of the different fractions were analyzed by quantitative electron microscopy. Normal-sized ECL cells from hypergastrinemic rats displayed a reduced number of secretory vesicles (probably because of degranulation) compared with normal-sized ECL cells from normogastrinemic rats. Hypertrophic ECL cells from hypergastrinemic rats had an unchanged number of secretory vesicles, supporting the view that such cells fail to respond to gastrin with degranulation. Although both normal-sized and hypertrophic ECL cells from hypergastrinemic rats contained vacuoles, those in the hypertrophic ECL cells were larger and more numerous. In addition, hypertrophic ECL cells were found to contain numerous, prominent lipofuscin bodies which are the presumed end product of crinophagia. Conceivably therefore, large vacuoles and lipofuscin bodies cause functional impairment of the hypertrophic ECL cells.
Zhao
C M
CM
Department of Laboratory Medicine, University Hospital of Trondheim, Norwegian University of Science and Technology, 7006 Trondheim, Norway. Chun-Mei.Zhao@medisin.ntnu.no
Bakke
I
I
Tostrup-Skogaker
N
N
Waldum
H L
HL
Håkanson
R
R
Chen
D
D
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002455:Cell Division; D048429:Cell Size; D019861:Enterochromaffin-like Cells / Q000648:ultrastructure*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D005755:Gastrins / Q000097:blood*; D006632:Histamine / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D006984:Hypertrophy; D008062:Lipofuscin / Q000096:biosynthesis*; D008854:Microscopy, Electron; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000648:ultrastructure; D013270:Stomach / Q000033:anatomy & histology*; D013454:Sulfoxides / Q000494:pharmacology; D013997:Time Factors; D014617:Vacuoles / Q000648:ultrastructure*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D005755:Gastrins; D008062:Lipofuscin; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D006632:Histamine; D000077402:Pantoprazole; D006640:Histidine Decarboxylase; D009853:Omeprazole