METABOLISM AND INFLUENCE OF GASTRIN-52 ON GASTRIC-ACID SECRETION IN HUMANS

It has been shown recently that the two largest alpha-carboxyamidated progastrin products are gastrin-71 and gastrin-52. Human gastrin-52 ha s now been synthesized, and the effect on gastric acid secretion and e limination from plasma was examined and compared with gastrin-17 in 12 normal subjects. The peptides were infused separately in four consecu tive doses; the maximum response of gastrin-17 and gastrin-52 was 25.2 +/- 2.8 and 22.2 +/- 2.8 mmol H+/50 min, respectively (P < 0.01). Thi s difference in efficacy was presumably related to nonequilibrium of g astrin-52 between plasma and receptor. The elimination of gastrin-17 w as monoexponential with a half-life of 4.7 +/- 0.3 min; clearance and apparent volume of distribution were 16.7 +/- 1.5 ml . kg(-1) . min(-1 ) and 106.0 +/- 9.2 ml/kg, respectively. The elimination of gastrin-52 was biexponential, the half-lives were 4.9 +/- 0.7 and 49.9 +/- 4.2 m in, and clearance and apparent volume of distribution were 1.9 +/- 0.2 ml . kg(-1) . min(-1) and 106.3 +/- 10.1 ml/kg, respectively. Gel chr omatography of plasma samples drawn during infusion of gastrin-52 reve aled that most of the immunoreactivity eluted in the position of the i ntact peptide. Small peaks in the positions of gastrin-34 and the NH2- terminal pentapeptide fragment of gastrin-52 indicate that a minor par t of gastrin-52 is degraded to smaller peptides in vivo. It is conclud ed that gastrin-52 is bioactive with an efficacy close to or similar t o that of gastrin-17. A minor fraction of gastrin-52 undergoes postsec retory cleavage either in plasma or after capillary transit.