OBJECTIVES: In addition to the acid-stimulatory gastrins, progastrin also release N-terminal fragments. In order to examine the cellular content, secretion and peripheral metabolism of these fragments, we developed an immunoassay specific for the N-terminal sequence of human progastrin.
RESULTS: The concentration of N-terminal progastrin fragments in human antral tissue was 6.7 nmol/g tissue (n=5), which was only half of that of acid-stimulatory gastrins (12 nmol/g tissue). Gel chromatography of antral extracts showed that the progastrin fragment 1-35 and 1-19 constitute the major part of the N-terminal progastrin fragments. The basal concentration of N-terminal fragments in normal human plasma was almost 30-fold higher than that of the amidated, acid-stimulatory gastrins (286 pmol/l versus 9.8 pmol/l, n=26, P<0.001). In contrast, the concentration of N-terminal fragments in hypergastrinemic plasma was only 2.7-fold higher than the concentration of amidated gastrins (540 pmol vs. 198 pmol/l, P=0.02). During meal stimulation, the plasma concentrations of N-terminal progastrin fragments and amidated gastrins increased in a correlated manner (r=0.97, P=0.005). The half life for progastrin 1-35 in circulation was 30 min, and a pig model revealed the kidneys and the vasculature to the head as the primary sites of degradation.
CONCLUSION: The cellular and circulatory concentration profiles of N-terminal progastrin fragments differ markedly from those of the acid-stimulatory gastrins. The high basal plasma concentrations of N-terminal progastrin fragments cannot be explained by differences in elimination.
|Status||Udgivet - 15 jan. 2006|