Gastrin and the Moderate Hypergastrinemias

Abstract

The antral hormone gastrin potently regulates gastric acid secretion and fundic mucosal growth. Consequently, appropriate gastrin secretion and plasma concentrations are important for the early phases of digestion. This review describes as the first premise the normal biogenesis of gastrin in the antral mucosa, but also mentions the extraantral expression. Subsequently, the molecular nature and concentration levels of gastrin in serum or plasma are overviewed. Third, assays for accurate measurements of plasma or serum concentrations are commented. Finally, the problem of moderate hypergastrinemia due to Helicobacter pylori infections and/or treatment with proton-pump inhibitors (PPI) is discussed. The review concludes that accurate measurement of the true concentrations of bioactive gastrins in plasma is important. Moreover, it suggests that moderate hypergastrinemias are also essential health issues that require serious attention.

Keywords: Helicobacter pylori; duodenal ulcer; gastric cancer; gastrin; hypergastrinemia; proton-pump inhibitors.

Figure 1

The structure of gastrin-17, the first identified molecular form of gastrin in antral G cells [15].

Figure 2

Scheme of processing steps for progastrin to release the two major bioactive gastrins, gastrin-17 and gastrin-34. Both forms are synthetized partly tyrosyl-sulfated. The endoproteolytic cleavages of progastrin are performed by prohormone convertases 1/3 and 2 [37,39].

Figure 3

Scheme of carboxyamidated products of preprogastrin. Endoproteolytic cleavage sites (R and K) are shown on preprogastrin. S and ns mean “sulfated” and “non-sulfated”, respectively.

Figure 4

Molecular forms of gastrin (−71, −34, −17 and −14) in normogastrinemic serum or plasma (upper panel) and in hypergastrinemic plasma (lower panel). Data from [38] with permission.

Figure 5

Meal-stimulated serum gastrin concentrations in duodenal ulcer patients with positive (CP+ve) or negative (CP–ve) biopsy urease tests for Helicobacter pylori. The arrow indicates the onset of the meal. From Levi et al. [18] with permission.