Regulation of Gastric Acid Secretion

Abstract

The actual presence of acid in gastric juice remained a scientific controversy for centuries. In 1826, William Beaumont made some fundamental observations in a patient with a posttraumatic gastric fistula. First, gastric juice was proven to be acidic and second, the rate of gastric acid secretion was not constant but appeared to be a highly regulated process controlled by food intake, emotions, and various other factors (1). The concept of regulation further evolved at the beginning of this century with the classical experiments by Pavlov and colleagues, who showed that taste, smell, and sight of food all stimulate acid secretion. They established that the central nervous system (CNS) plays an important role in the initial phase of acid secretion (2). At the same time, the concept of endocrine regulation via “hormones” was created by Bayliss and Starling (3). The idea started in the small intestine, as an extractable mucosal “active principle” named “secretin” that stimulates pancreatic bicarbonate secretion, but gained relevance later also for the stomach as a potential “enterogastrone,” a gut factor that inhibits gastric acid secretion (4,5). Endocrinology soon approached the stomach directly: Edkins postulated in 1905 the existence of a chemical factor in the antral mucosa, designated gastrin, that stimulates acid output after intravenous injection (6). The discovery of histamine, another potent acid secretagog (7) also present in the gastric mucosa, shed some doubt on the actual existence of gastrin as a separate entity until Gregory and Tracy in 1964 isolated and sequenced two molecular forms of the antral peptide, gastrin (8). This work marked the beginning of the chemical era of gastrointestinal hormones and represented a cornerstone in gastric endocrinology (9).