Trophic role of CCK B-gastrin receptors in intact and ulcerated oxyntic mucosa in rats

Abstract

Background: The trophic role of CCK B-gastrin receptors (GR) in the intact and ulcerated gastric oxyntic mucosa is not entirely clear. The proton pump inhibitor omeprazole (OME) causes acid inhibition and hypergastrinemia and causes growth promoting effects on the oxyntic mucosa (Schmassmann et al., Gastroenterology 1997; 133: No. 12). We speculated that the GR antagonist YF476 which also causes acid-inhibition and hyper-gastrinemia, would not have such effects due to YF476-induced inhibition of gastrin-GR interactions on stem cells. Methods: We assessed the time-sequence of CCK B-gastrin receptors (mRNA and protein) after cryoinjury of the oxyntic rat mucosa. Furthermore, 96 rats were treated with placebo (PLA), OME (40 lamol/kg-day), YF476 (100 ~mol/kg-day) and OME+YF476 for 3, 8 and 15 days. Epithelial cell proliferation was assessed in the intact and ulcerated oxyntic mucosa. Res.ults: Whereas GR mRNA and protein were down-regulated on day 3, GR protein was up-regulated on days 8 and 15. Compared with PLA, OME, YF476 and OME+YF476 caused a > four-fold increase of serum gastrin on days 3, 8 and 15 and a > two-fold decrease of ulcer size on day 15. OME increased (P < 0.01) epithelial cell proliferation in the ulcer margin on days 3, 8 and 15 by 23, 30 and 46%, respectively and in the intact mucosa (day 15) by 22%. In contrast, YF476 had no significant effect on epithelial cell proliferation in the intact or ulcerated mucosa. OME-induced effects on epithelial cell proliferation were partly reversed by co-therapy with YF476. Conclusion: The proton pump inhibitor omeprazole but not the gastrin receptor antagonist YF476 have trophic effects on the intact and ulcerated oxyntic mucosa. Our data suggest atrophic role of CCK B-gastrin receptors both in the intact and ulcerated oxyntic mucosa. Supported by the Swiss National Science Foundation (32-51099.97)