From Prout to the proton pump--a history of the science of gastric acid secretion and the surgery of peptic ulcer.

Prior to the 17th century, there was considerable confusion regarding the process of digestion. Although some physicians were certain that it was initiated by acid in the stomach, both the source and the nature of the acid were unclear. In the early 19th century, Prout confirmed the active secretion of hydrochloric acid by the stomach and related it to the symptoms of dyspepsia. Jacob Helm and, subsequently, Beaumont studied digestion in humans with gastric fistulas and each commented extensively on the physiologic manifestation of digestion. The role of the vagus nerves in the control of gastric acid secretion was identified in the early and mid-19th century by Brodie, and subsequently elaborated upon by Pavlov. By the early 20th century, Latarjet and Jaboulay in France, performing operations for abdominal pain and tabes, reported the effects of vagotomy on acid secretion and gastric motility. In 1943, Dragstedt, in the United States, reported the cure of duodenal peptic ulcer disease by supradiaphragmatic vagotomy. He later observed the substantial delays in emptying of the stomach, which necessitated the introduction of concomitant gastric drainage procedures, such as gastrojejunostomy and pyloroplasty. In 1902, Bayliss and Starling had described the existence of a chemical regulator of function--secretin--which they termed a hormone. Shortly thereafter, Edkins reported results of studies that supported the presence of an acid regulatory hormone, gastrin, in the antrum of the stomach. Unfortunately, controversy marred this observation, and the action of gastrin was for more than 30 years ascribed to histamine. Komarov, in 1938, confirmed the existence of gastrin and its stimulatory effects on acid secretion. Physiologic recognition of the roles of vagal stimulation and antral gastrin in the secretion of acid from the stomach resulted in the development of the operation of vagotomy and antrectomy for peptic ulcer disease. Studies of the pylorus and the motility of the stomach resulted in an appreciation of the genesis of the postgastrectomy syndromes. By the middle of the 20th century, a clear appreciation of the morphologic characteristics of the parietal cell and its ability to secrete hydrochloric acid was under way. The complex metabolic process of the cell was correlated with the major morphologic transformation necessary to generate secretion of hydrochloric acid. The development of sophisticated research technology allowed the appreciation of the complex intracellular processes necessary to allow the generation of a 2.5 million-fold gradient of hydrogen ion secretion.(ABSTRACT TRUNCATED AT 400 WORDS)