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

8 Citations (Scopus)

Abstract

The antral hormone gastrin is synthesized by processing progastrin into different peptides that stimulate gastric secretion. The effect on acid secretion depends mainly on the metabolic clearance rate of the peptides, but some of them may differ in potency and maximum acid output at similar concentrations in plasma. Sulfated and nonsulfated gastrin-6 are the smallest circulating bioactive gastrins in humans. Their effect and metabolism have now been investigated in nine normal subjects and compared with nonsulfated gastrin-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 EC(50) 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 significantly from gastrin-17 (P < 0.01). We conclude that gastrin 6 has a higher potency but a lower efficacy than gastrin-17. The efficacy of gastrin-6 is increased by tyrosine O-sulfation, which also enhances the protection against elimination.

Original languageEnglish
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Volume279
Issue number5
Pages (from-to)G903-9
ISSN0193-1857
DOIs
Publication statusPublished - Nov 2000

Keywords

  • Adult
  • Chromatography, Gel
  • Female
  • Gastric Acid/metabolism
  • Gastric Mucosa/metabolism
  • Gastrins/blood
  • Humans
  • Male
  • Peptide Fragments/blood
  • Pyloric Antrum/metabolism
  • Sulfates/blood

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