Effects of CCK2 receptor blockade on growth parameters in gastrointestinal tract and pancreas in rats

Gastrin has a growth-promoting effect on the oxyntic mucosa of the stomach but has been claimed also to affect other parts of the gastrointestinal tract and pancreas. This report describes the effects of the cholecystokinin, (CCK2) receptor antagonists YM022 and YF476 on various growth parameters in the gastrointestinal tract and pancreas of the rat. YM022 and YF476 were given subcutaneously in doses known to produce maximum and sustained CCK2 receptor blockade. The body weight was not affected. However, the oxyntic mucosal weight, thickness and protein and DNA contents were reduced by 15-20% already within 1-2 days and by about 30% after 4-8 weeks of CCK2 receptor blockade. Hence, the response of the oxyntic mucosa to CCK2 receptor blockade was in the form of hypotrophy (reduced protein content) and hypoplasia (reduced DNA content). There were no obvious effects of CCK2 receptor blockade on the intestine or pancreas (nor on liver, kidney or thyroid). The proton pump inhibitor omeprazole was used to induce hypergastrinaemia and was given with or without YM022. Omeprazole treatment for 4 weeks increased the oxyntic mucosal weight and thickness by 15-20%. YM022 prevented these effects. We conclude that while elevated circulating gastrin levels, acting on CCK2 receptors, exert a growth-promoting effect on the oxyntic mucosa (but not elsewhere), normal serum gastrin levels exert a mucosa-preserving effect.