title: Rebound acid hypersecretion from a physiological, pathophysiological and clinical viewpoint.
abstract: OBJECTIVE
  The recent description of dyspepsia in healthy individuals after stopping treatment with proton-pump inhibitors (PPIs) indicates that reflux disease may worsen due to this treatment. The aim of this paper is to review current knowledge of the regulation of gastric acid secretion, including maximal acid secretion, and to improve understanding of the pathogenesis of acid-related conditions.
  
  
  METHODS
  We reviewed our findings from three decades of studies on gastric acid secretion in the isolated rat stomach and in humans as well as studies by the group of Robert Jensen involving gastrinoma patients.
  
  
  RESULTS
  The parietal cell has receptors for histamine and acetylcholine, whereas the gastrin receptor is localized to the enterochromaffin-like (ECL) cell. Gastrin-stimulated histamine release depends on the ECL cell mass, which is regulated by gastrin. The parietal cell mass is also influenced by gastrin. All conditions with hypergastrinemia concomitant with a normal oxyntic mucosa result in an increase in acid secretion. Helicobacter pylori infection in the antral mucosa may induce duodenal ulcers by its effect on acid secretion, as in patients with gastrinoma. Whereas PPIs induce clinically important rebound acid hypersecretion, histamine-2 blockers do not, since they also induce tolerance.
  
  
  CONCLUSIONS
  From a biological and physiological point of view, patients should be given treatment that disturbs the normal physiology as little as possible.
authors.affiliation: Department of Gastroenterology and Liver Diseases, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. helge.waldum@ntnu.no
authors.forename: Helge L
authors.initials: HL
authors.lastname: Waldum
authors.forename: Gunnar
authors.initials: G
authors.lastname: Qvigstad
authors.forename: Reidar
authors.initials: R
authors.lastname: Fossmark
authors.forename: Per M
authors.initials: PM
authors.lastname: Kleveland
authors.forename: Arne K
authors.initials: AK
authors.lastname: Sandvik
mesh_terms: D000818:Animals; D004415:Dyspepsia / Q000209:etiology*; D019861:Enterochromaffin-like Cells / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism*; D015408:Gastrinoma / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori; D006632:Histamine / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage; D006801:Humans; D010295:Parietal Cells, Gastric / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D051381:Rats; D013274:Stomach Neoplasms / Q000378:metabolism
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D006632:Histamine