Gastrin mediates the increase in gastric cell growth in uremic rats.
In a rat model of chronic renal failure, we recently reported that hypergastrinemia was associated with increased stomach weight and parietal cell and enterochromaffin-like (ECL) cell density. In this study, the role of gastrin in mediating trophic effects of uremia on the gastric mucosa was examined by chronic immunoneutralization of endogenous gastrin in the sub-total nephrectomy uremic rat model. Three weeks after surgery, the rats were uremic (azotemic and hypertensive). Uremic rats had a significant increase in corpus mucosal height (17%), parietal cell density (14%), ECL cell density (27%), and basal gastric mucosal blood flow (63%). These effects were specifically inhibited by chronic administration of gastrin-specific monoclonal antibody (5 mg ip every other day) in the 3-wk postoperative period. Uremic rats also had an increase in stomach weight (23%), corpus mucosal area (8%), arterial blood pressure, and serum creatinine and a decrease in body weight. Gastrin immunoneutralization did not alter these effects. The findings suggest that elevated levels of endogenous circulating gastrin in uremic rats mediate, in part, the trophic response observed in the gastric mucosa.
Quintero
E
E
Research Service, Department of Veteran Affairs, Los Angeles, California 90073, USA.
Ohning
G V
GV
Del Rivero
M
M
Wong
H C
HC
Walsh
J H
JH
Guth
P H
PH
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002455:Cell Division; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply; D005755:Gastrins / Q000276:immunology / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013270:Stomach / Q000473:pathology*; D014511:Uremia / Q000473:pathology* / Q000503:physiopathology*
D000906:Antibodies; D005755:Gastrins