Antral content, secretion and peripheral metabolism of N-terminal progastrin fragments.
OBJECTIVE
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.


CONCLUSIONS
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.
Goetze
Jens Peter
JP
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark. JPG@dadlnet.dk
Hansen
Carsten Palnaes
CP
Rehfeld
Jens F
JF
D000818:Animals; D002219:Carbamates / Q000737:chemistry* / Q000378:metabolism; D002850:Chromatography, Gel; D005755:Gastrins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011863:Radioimmunoassay; D013552:Swine; D013997:Time Factors
C091590:Antral; D002219:Carbamates; D005755:Gastrins; D009942:Organometallic Compounds; D011498:Protein Precursors; C013706:big gastrin