Secretion and biosynthesis of COOH-terminal glycine extended progastrin (gastrin-G) in rat gastric antrum

Abstract

The effects of serotonin (5-HT) on gastrin and COOH-terminal glycine extended progastrin (gastrin-G) secretion, biosynthesis of gastrin and gastrin-G, and the effects of gastrin-G on gastric acid secretion were examined in rats. 5-HT 10(-5) M significantly stimulated gastrin and gastrin-G secretion. Atropine 10(-6) M, which abolished the effects of cholinergic agent to stimulate gastrin secretion, blocked the 5-HT-stimulated gastrin and gastrin-G secretion. In biosynthesis of gastrin and gastrin-G the peak of 35S radioactivity appeared in gastrin-G immunoreactive peak at 30 minutes incubation, however, 35S radioactivity did not appear in the gastrin immunoreactive peak until 1 hour chase incubation. The peak of 35S radioactivity transferred from the gastrin-G immunoreactive peak to the gastrin immunoreactive peak. Concerning the bioactivity of gastrin-G, it did not stimulate gastric acid secretion. From these findings we may conclude that serotoninergic neurons act as interneurons which themselves stimulate a second neuron stimulatory to gastrin and gastrin-G secretion, the posttranslational processing of gastrin occurs sequentially through the proteolytic processing of progastrin to glycin extended processing intermediates, gastrin-G, followed by activation via alpha-amidation in secretory granules, gastrin-G co-secreted with gastrin does not have biological activity, PAM activity in serum does not play a functional role under physiological conditions.