GRP and Pavlov's dogs.

The cephalic phase of gastric acid secretion has been a topic of great interest to physiologists and physicians since its description by Pavlov 100 years ago. 1 In classic " sham " feeding studies performed on dogs equipped with an oesophageal stoma and a gastric fistula, Pavlov demonstrated that food was a prompt and powerful stimulant of gastric secretion. This stimulation occurred despite the fact that the ingested food entered the dog's mouth and pharynx and exited through the stoma, never actually reaching the stomach. Pavlov went on to demonstrate that severing the vagus nerves just above the diaphragm abolished the gastric acid secretory response to sham feeding in dogs. His experiments demonstrated that sham feeding elicited a potent gastric acid secretory response via the vagus nerves. Although experiments involving surgically created fistu-las could not be conducted in humans, in the 1970s Knut-son and Olbe developed a " modified " sham feeding technique to study the cephalic phase of gastric acid secretion in patients with duodenal ulcer disease. 2–4 Patients chewed and expectorated appetising food without swallowing it, and a tube inserted into the stomach collected gastric fluid for acid analysis. Using modified sham feeding in healthy volunteers, Richardson et al demonstrated that the cephalic phase of gastric acid secretion accounted for half of the acid secreted during the first postprandial hour. 5 The thought and taste of food were more important secretory stimulants than the sight or smell of a meal. 6 Acetylcholine and histamine were demonstrated to be important mediators of the cephalic phase of gastric acid secretion in humans because injection of either the muscarinic antagonist atropine or the histamine H 2 receptor antagonist cime-tidine markedly attenuated the acid secretory response to modified sham feeding. 7 8 Much as Pavlov had demonstrated in dogs, clinical investigators found that the cephalic phase of gastric acid secretion in humans could also be abolished by surgical vagotomy, even by a proximal selective vagotomy which preserved the vagal innervation of the gastric antrum and pylorus. 2 9 The antral hormone gastrin is released into the blood during the cephalic phase of gastric acid secretion in humans. 4–7 9 10 Although the amount of gastrin released during modified sham feeding is small in comparison with the amount released during normal eating, the serum increase in gastrin probably contributes to a substantial proportion of the acid secreted during modified sham feeding. In contrast …