Much ado about gastrin.

The regulation of gastrin secretion from antral G-cells is of major importance in the physiologic control of acid secretion. Gastrin secretion is highly dependent upon gastric intraluminal pH and is inhibited significantly by a pH of less than 3.0. Acute gastric alkalinization greater than pH 6.0 with antisecretory agents such as H2-receptor antagonists or H+/K+ ATPase inhibitors has little impact on fasting serum gastrin levels but promotes an enhanced sustained rise in meal-stimulated gastrin release. Courses of standard therapy with both H2-antagonists and H+/K+ inhibitors cause a significant rise in 24 h integrated plasma gastrin levels that is inversely correlated to the 24-h integrated gastric acidity. The rise in fasting or integrated plasma gastrin levels observed in patients treated with H2-antagonists is small and of unclear clinical significance. Therapy with antisecretory agents leads to earlier ulcer relapse than with other agents. A variety of factors have been proposed to explain the earlier ulcer relapse rate, including secondary hypergastrinemia with rebound acid hypersecretion after discontinuation of the drug. Secondary hypergastrinemia may also lead to tolerance to prolonged courses of H2-antagonists therapy with a decrease in acid inhibition. This may contribute to break-through ulcer recurrence during maintenance H2-antagonist therapy. However, the relative importance of hypergastrinemia and tolerance to H2-antagonists compared with other factors such as baseline gastric acid secretion, smoking status, nonsteroidal anti-inflammatory drug use, and Helicobacter pylori status is difficult to assess.(ABSTRACT TRUNCATED AT 250 WORDS)