Biology and pathology of non-amidated gastrins.

The regulation and extent of progastrin processing has assumed greater importance with the realisation that progastrin and its processing intermediates have functions quite separate from the biosynthetic end product gastrin-amide. The pattern of processing products generated are organ and disease specific with amidated forms predominating in the stomach and non-amidated forms being more important in colorectal carcinoma. In the stomach, non amidated gastrins sustains the acid stimulatory effect of gastrin amide on gastric acidity. The proliferation of colorectal carcinomas and cell lines are stimulated by nonamidated gastrins presumably by an autocrine regulatory loop acting through distinct receptors. The potential role of non-amidated gastrins as therapeutic targets will remain uncertain until the nature of the receptors are determined and specific antagonists developed.