Metabolism and influence of glycine-extended gastrin on gastric acid secretion in man.
Glycine-extracted gastrins are the immediate precursors of the bioactive carboxyamidated gastrins. The effect on gastric acid secretion and the pharmacokinetics of glycine-extended gastrin-17 were studied in 8 normal subjects. The elimination in plasma after bolus injection was biexponential, the half-lives being 4.1 +/- 0.2 and 21.8 +/- 0.9 min, and clearance and apparent volume of distribution being 7.9 +/- 0.6 ml/kg/min and 69.5 +/- 2.7 ml/kg, respectively. Infusion of the peptide at three consecutive dose rates did not stimulate gastric acid secretion, although plasma concentrations reached supraphysiological levels. Nor did glycine-extended gastrin-17 influence submaximal acid secretion induced by amidated gastrin-17. In contrast to amidated gastrins, the concentration of glycine-extended gastrins in peripheral venous plasma did not increase significantly after a meal. The postprandial rise in amidated gastrin was unaffected by concomitant infusion of glycine-extended gastrin-17. A reduction in glycine-extended gastrin-17 concentrations in plasma during constant-rate infusion of the peptide was observed after a protein meal (p < 0.05). This reduction was reflected by an increase in glycine-extended gastrin-17 is without immediate effect on gastric output in man. The postprandial increase in clearance might be due to increased splanchnic blood flow with subsequently increased peptide elimination.
Palnaes Hansen
C
C
Department of Gastrointestinal Surgery, Righospitalet, University of Copenhagen, Denmark.
Stadil
F
F
Rehfeld
J F
JF
D000328:Adult; D002850:Chromatography, Gel; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male
D005755:Gastrins; C086854:glycine-extended gastrin 17