METABOLISM AND INFLUENCE OF GLYCINE-EXTENDED GASTRIN ON GASTRIC-ACID SECRETION IN MAN

Glycine-extended gastrins are the immediate precursors of the bioactiv e carboxyamidated gastrins. The effect on gastric acid secretion and t he pharmacokinetics of glyine-extended gastrin-17 were studied in 8 no rmal subjects. The elimination in plasma after bolus injection was bie xponential, 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 i nduced by amidated gastrin-17. In contrast to the amidated gastrins, t he concentration of glycine-extended gastrins in peripheral venous pla sma 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 conce ntrations in plasma during constant-rate infusion of the peptide was o bserved after a protein meal (p < 0.05). This reduction was reflected by an increase in clearance rate of 80% (p < 0.05). Our investigations demonstrate that glycine-extended gastrin-17 is without immediate eff ect on gastric output in man. The postprandial increase in clearance m ight be due to increased splanchnic blood flow with subsequently incre ased peptide elimination.