Metabolism of heptadecapeptide gastrin in humans studied by region-specific antisera.
The metabolism of synthetic human heptadecapeptide gastrin (G17) in vivo, and in serum in vitro, was studied by radioimmunoassay using region specific antisera, gel filtration, ion exchange chromatography, and high performance liquid chromatography. After infusion of G17 intravenously in normal human volunteers, COOH-terminal and NH2-terminal immunoreactive G17 fragments were generated. At a steady state, approximately 15% of COOH-terminal immunoreactivity was attributable to G14-like material and up to 25% of total NH2-terminal immunoreactivity was attributable to two NH2-terminal fragments; one had the chromatographic properties of 1-13 G17, and the other was less acidic and less hydrophobic. After stopping the infusion of G17, the latter fragments accounted for progressively greater proportions of total gastrin activity. When G17 was incubated in serum in vitro, there was time-dependent and temperature-dependent loss of immunoreactivity, and again COOH-terminal and NH2-terminal immunoreactive fragments were formed. Removal of the NH2-terminal pyroglutamic acid was probably the rate limiting step because synthetic 2-17 G17 was degraded more rapidly in serum (t1/2, 2-3 h) than G17 (t1/2, 3-5 h). EDTA blocked degradation at the COOH-terminus of both 2-17 G17 and G17 but cleavage at the NH2-terminus still occurred, giving rise to a G14-like peptide. The rate of conversion of G17 in serum was not enough to account for the production of fragments in vivo, and it is proposed that these are formed when G17 encounters enzymes on cell surfaces, perhaps during passage through the capillary circulation. The production of these fragments needs to be considered in interpreting studies of the identity, metabolism, and release of gastrin in health and disease.
Pauwels
S
S
Dockray
G J
GJ
Walker
R
R
Marcus
S
S
D000328:Adult; D000595:Amino Acid Sequence; D004492:Edetic Acid / Q000494:pharmacology; D000939:Epitopes; D005755:Gastrins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism; D011863:Radioimmunoassay
D000939:Epitopes; D005755:Gastrins; D010446:Peptide Fragments; D004492:Edetic Acid