Ottewell, P.D.; Watson, A.J.M.; Wang, T.C.; Varro, A.; Dockray, G.J.; Pritchard, D.M.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA8
Academic Journal
Background and Aims: Amidated gastrin has well characterised mitogenic and morphogenic properties in the stomach, but its role in the distal intestine remains unclear. We have previously demonstrated no differences in the levels of apoptosis and mitosis in small intestinal and colonic epithelia of mice that overexpress amidated gastrin (INSGAS) compared to their wild-type counterparts, either in the untreated state or 4.5 hours following 8 Gy γ radiation. In order to complete our analysis of the effects of hypergastrinaemia upon the distal intestine in vivo, we have now investigated the effects of elevated plasma concentrations of amidated gastrin upon intestinal crypt survival following γ radiation. Methods: Mice analysed were adult INS-GAS and their wild-type counterparts (FVB/N). CIonogenic crypt survival was assessed by light microscopy of small intestinal and colonic crypts four days after 10, 12, or 14Gy γ radiation. We confirmed that the differences observed were specifically induced by hypergastrinaemia by analysing INS-GAS mice treated with the specific gastrin/CCKB receptor antagonist YF476 and FVB/N mice treated with omeprazole. Results: Four days following 12 and 14Gy γ radiation, INS-GAS mice exhibited significantly higher (∼3 fold) small intestinal and colonic crypt survival compared with their wild-type counterparts. INSGAS mice treated with YF476 showed significantly lower (∼4 fold) small intestinal and colonic crypt survival after 14Gy γ radiation compared with mice receiving vehicle alone. FVB/N mice dosed with omeprazole to induce hypergastrinaemia showed significantly increased (∼4 fold) survival of small intestinal and colonic crypts after 14Gy γ radiation. Conclusions: (a) Increased small intestinal and colonic crypts survival is observed in mice with elevated plasma concentrations of amidated gastrin following γ radiation. (b) This protective effect of hypergastrinaemia occurs as a...


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