Glycine-extended progastrin processing intermediates: accumulation and cosecretion with gastrin.

Area of Science:

• Endocrinology
• Cell Biology
• Gastroenterology

Background:

• Peptide hormones, like gastrin, are often activated by carboxyl-terminal amidation.
• Glycine-extended peptides are precursors to amidated, active forms.
• G-cells in the gastric antrum produce and secrete gastrin.

Purpose of the Study:

• To investigate the accumulation and secretion dynamics of glycine-extended progastrin intermediates (G-Gly).
• To explore the role of ascorbate in G-Gly processing and gastrin homeostasis.
• To determine if amidation is essential for gastrin secretion.

Main Methods:

• Primary culture of canine antral G-cells.
• Culture in ascorbate-deficient and ascorbate-supplemented media.
• Measurement of G-Gly and gastrin levels over time.
• Stimulation and inhibition of secretion with bombesin and somatostatin.
• Electron microscopy of G-cells.

Main Results:

• G-cells in ascorbate-deficient media showed rapid G-Gly accumulation and gastrin degradation.
• G-cells in ascorbate-supplemented media maintained higher gastrin levels and slower G-Gly accumulation.
• Both G-Gly and gastrin were secreted and their release was modulated by bombesin and somatostatin.
• No ultrastructural changes were observed in cultured G-cells.

Conclusions:

• Cellular G-Gly homeostasis is regulated by an ascorbate-dependent amidation enzyme.
• Carboxyl-terminal amidation is not required for gastrin secretion.
• The ratio of secreted gastrin to G-Gly reflects their intracellular proportions.
• The physiological significance of secreted G-Gly requires further investigation.