Hypergastrinemia in response to gastric inflammation suppresses somatostatin.
Hypergastrinemia and a reduction in tissue somatostatin occur in Helicobacter pylori-infected patients. We investigated whether the D cell may be a direct target of gastric inflammation and hypergastrinemia. D cells were quantified by morphometry and flow cytometry in 16-wk-old wild-type (G+/+) and gastrin-deficient (G-/-) mice. Hypochlorhydric G-/- mice were treated with either antibiotics for 20 days or infused with gastrin (G-17) for 14 days. G+/+ mice were made hypochlorhydric by treating them with omeprazole for 2 mo. G-/- mice showed significant inflammation compared with the G+/+ mice, which resolved after 20 days of antibiotic treatment. D cell numbers were not significantly different between G-/- and G+/+ mice. After G-17 was infused, fundic and antral D cell numbers decreased in the G-/- mice. G+/+ animals made hypergastrinemic with omeprazole exhibited decreased D cell numbers. When omeprazole-treated mice were treated with antibiotics alone, elevated plasma gastrin levels returned to baseline and D cell numbers returned to resting levels despite persistent hypochlorhydria. Hypergastrinemia, induced by inflammation, results in decreased D cell numbers. Thus the stomach responds to the presence of inflammation by reducing somatostatin levels, thereby releasing the inhibition on the G and parietal cells to maximize gastric acid output.
Zavros
Yana
Y
Howard Hughes Medical Institute, Ann Arbor, Michigan 48109-0650, USA.
Rieder
Gabriele
G
Ferguson
Amy
A
Samuelson
Linda C
LC
Merchant
Juanita L
JL
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005748:Gastric Fundus / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology; D005755:Gastrins / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D016481:Helicobacter Infections / Q000378:metabolism / Q000503:physiopathology*; D016480:Helicobacter pylori; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009853:Omeprazole / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011706:Pyloric Antrum / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D013004:Somatostatin / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D005755:Gastrins; D013004:Somatostatin; C013550:gastrin 17; D009853:Omeprazole