The Discovery of Gastrin

Overview

Gastrin is a family of peptide hormones produced by G-cells in the gastric antrum and, to a lesser extent, in the duodenum. It was first proposed in 1905 by John Sydney Edkins, a British physiologist who showed that extracts of the gastric mucosa could stimulate gastric acid secretion when injected into animals. Edkins named the active principle "gastric secretin" — or gastrin — by analogy with secretin, discovered three years earlier.

Edkins's claim was controversial. For decades, some physiologists argued that the stimulatory activity in his extracts was due to histamine contamination rather than a distinct hormone. The question was not definitively resolved until the 1960s, when Roderic Gregory and Hilda Tracy at the University of Liverpool purified gastrin from hog antral mucosa and determined its structure: initially a 17-amino-acid peptide (gastrin-17), later complemented by a 34-amino-acid form (gastrin-34).

Gastrin's C-terminal sequence is closely related to that of cholecystokinin, and both peptides share a common receptor (CCK2, formerly CCK-B/gastrin). Gastrin stimulates parietal cells to secrete hydrochloric acid, promotes the growth of the gastric mucosa, and has trophic effects on enterochromaffin-like (ECL) cells.

Key People

• John Sydney Edkins (1863–1940): British physiologist who proposed gastrin in 1905.
• Roderic A. Gregory (1913–1990): British physiologist who purified gastrin at Liverpool.
• Hilda J. Tracy: Gregory's long-time collaborator and co-author on gastrin purification.
• Morton I. Grossman: American gastroenterologist who championed gastrin research mid-century.
• Robin Warren and Barry Marshall: 2005 Nobel laureates whose work on Helicobacter pylori reshaped understanding of gastrin dysregulation.

Timeline

• 1905: Edkins proposes gastrin.
• 1920s–1950s: Disputes over whether gastric extracts act via histamine or a true hormone.
• 1964: Gregory and Tracy purify porcine gastrin-17.
• 1966: Gastrin-34 is identified.
• 1973: Zollinger-Ellison syndrome is characterized as gastrinoma-driven hyperacidity.
• 1983: Marshall and Warren describe Helicobacter pylori in gastric mucosa.
• 1990s: H2-blockers and proton pump inhibitors dominate acid-related disease therapy.
• 2000s: Gastrin receptor (CCK2) cloned; targeted imaging and therapy developed.

Background

Gastrin is released primarily in response to protein-rich meals, gastric distension, and vagal stimulation through gastrin-releasing peptide (GRP/bombesin). It acts on parietal cells directly via CCK2 receptors and indirectly through histamine release from ECL cells. Acid secretion in turn feeds back to suppress gastrin via somatostatin-producing D-cells.

Disorders of gastrin signaling have major clinical consequences. Zollinger-Ellison syndrome, caused by gastrin-secreting neuroendocrine tumors (gastrinomas), produces severe peptic ulcer disease and diarrhea. Chronic atrophic gastritis, often associated with H. pylori infection or autoimmune disease, can cause reactive hypergastrinemia because acid-mediated suppression is lost. Prolonged use of proton pump inhibitors also raises gastrin levels modestly, a subject of ongoing clinical research.

Modern Relevance

Measurement of serum gastrin is an essential test in the evaluation of suspected gastrinoma and of unexplained hypochlorhydria. CCK2 receptor-targeted radiopharmaceuticals are being developed for imaging and peptide receptor radionuclide therapy of medullary thyroid carcinoma and gastrinomas.

Gastrin continues to be a model for studying the regulation of peptide hormones by negative feedback loops and for understanding the consequences of chronic receptor activation. Its intersection with H. pylori biology, proton pump inhibitor therapy, and gut-brain axis research keeps gastrin relevant nearly 120 years after Edkins first proposed its existence. For related gut peptides, see cck-discovery and secretin-first-hormone.

Related Compounds

• Gastrin
• CCK
• Somatostatin
• Ghrelin
• GRP / Bombesin