Effect of cholecystokinin-2 receptor blockade on rat stomach ECL cells. A histochemical, electron-microscopic and chemical study.
The ECL cells in the oxyntic mucosa of rat stomach produce histamine and chromogranin A-derived peptides such as pancreastatin. The cells respond to gastrin via cholecystokinin-2 (CCK2) receptors. A CCK2 receptor blockade was induced by treatment (for up to 8 weeks) with two receptor antagonists, YM022 and YF476. Changes in ECL-cell morphology were examined by immunocytochemistry and electron microscopy, while changes in ECL cell-related biochemical parameters were monitored by measuring serum pancreastatin and oxyntic mucosal pancreastatin, and histamine concentrations, and histidine decarboxylase (HDC) activity. The CCK2 receptor blockade reduced the ECL-cell density only marginally, if at all, but transformed the ECL cells from slender, elongated cells with prominent projections to small, spherical cells without projections. The Golgi complex and the rough endoplasmic reticulum were diminished. Secretory vesicles were greatly reduced in volume density in the trans Golgi area. Circulating pancreastatin concentration and oxyntic mucosal HDC activity were lowered within a few hours. Oxyntic mucosal histamine and pancreastatin concentrations were reduced only gradually. The CCK2 receptor blockade was found to prevent the effects of omeprazole-evoked hypergastrinaemia on the ECL-cell activity and density. In conclusion, gastrin, acting on CCK2 receptors, is needed to maintain the shape, size and activity of the ECL cells, but not for maintaining the ECL-cell population.
Chen
D
D
Department of Pharmacology, University of Lund, Sweden.
Zhao
C M
CM
Norlén
P
P
Björkqvist
M
M
Ding
X Q
XQ
Kitano
M
M
Håkanson
R
R
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D053379:Chromogranin A; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000648:ultrastructure; D005755:Gastrins / Q000097:blood; D006632:Histamine / Q000032:analysis; D006640:Histidine Decarboxylase / Q000032:analysis; D006727:Hormone Antagonists / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009853:Omeprazole / Q000494:pharmacology; D010187:Pancreatic Hormones / Q000097:blood; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D010671:Phenylurea Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013997:Time Factors
D001570:Benzodiazepinones; D053379:Chromogranin A; D005755:Gastrins; D006727:Hormone Antagonists; D010187:Pancreatic Hormones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C050836:pancreastatin; D001569:Benzodiazepines; C087260:YM 022; D006632:Histamine; D006640:Histidine Decarboxylase; C104428:YF 476; D009853:Omeprazole