Biosynthesis of gastrin. Localization of the precursor and peptide products using electron microscopic-immunogold methods.

Antibodies to different peptides produced from the gastrin precursor have been used in light microscopic- and electron microscopic-immunogold studies of gastrinoma tissue and normal antral mucosa. Antibodies to the C terminus of progastrin, which are known to react with the intact precursor, revealed immunoreactive material in the rough endoplasmic reticulum, Golgi region, and electron-dense granules in gastrinoma cells. In normal antrum these antibodies again revealed the Golgi region and a population of electron-dense granules. Other antibodies that react with the products of progastrin processing, but not the precursor, e.g., C-terminal and N-terminal gastrin 17 specific antibodies, revealed only granules. In addition to electron-dense granules already mentioned, the latter antibodies also revealed electron-lucent and intermediate granule populations, which in antrum were the major granule types. It is proposed that the intact precursor occurs in rough endoplasmic reticulum and Golgi; thereafter, in the immature electron-dense granules, and subsequently in electron-lucent granules, biosynthetic processing liberates gastrin 17 and gastrin 34, which are the major active products of gastrin gene expression.