Metabolism and acid secretory effect of sulfated and nonsulfated gastrin-6in humans

The antral hormone gastrin is synthesized by processing progastrin into dif ferent peptides that stimulate gastric secretion. The effect on acid secret ion depends mainly on the metabolic clearance rate of the peptides, but som e of them may differ in potency and maximum acid output at similar concentr ations in plasma. Sulfated and nonsulfated gastrin-6 are the smallest circu lating bioactive gastrins in humans. Their effect and metabolism have now b een investigated in nine normal subjects and compared with nonsulfated gast rin-17, a main product of progastrin. Maximum acid output after stimulation with gastrin-17, sulfated gastrin-6, and nonsulfated gastrin-6 were 28.3 /- 2.0, 24.5 +/- 2.0 (P < 0.02), and 19.3 +/- 2.3 (P < 0.05) mmol H+/50 min , respectively, and the corresponding EC50 values were 43 +/- 6, 24 +/- 2 ( P < 0.01), and 25 +/- 2 (not significant) pmol/l. The half-life of gastrin- 17 was 5.3 +/- 0.3 min, the metabolic clearance rate (MCR) was 16.5 +/- 1.3 ml.kg(-1).min(-1), and the apparent volume of distribution (V-d) was 124.3 +/- 9.6 ml/kg. The half-lives of sulfated and nonsulfated gastrin-6 were 2 .1 +/- 0.3 and 1.9 +/- 0.3 min, the MCRs were 42.8 +/- 3.7 and 139.4 +/- 9. 6 ml kg(-1) min(-1) (P < 0.01), and the V-d were 139.0 +/- 30.5 and 392.0 /- 81.6 (P < 0.01) ml kg(-1). All pharmacokinetic parameters differed signi ficantly from gastrin-17 (P < 0.01). We conclude that gastrin 6 has a highe r potency but a lower efficacy than gastrin-17. The efficacy of gastrin-6 i s increased by tyrosine O-sulfation, which also enhances the protection aga inst elimination.