title: Review article: the pharmacological inhibition of gastric acid secretion--tolerance and rebound.
abstract: During the last decade our understanding of the regulation of gastric acid secretion has changed considerably. The recognition that gastrin acts mainly by releasing histamine from the enterochromaffin-like (ECL) cell is of major importance. It is now necessary to review and seek new explanations for the development of tolerance and for the post-treatment acid hypersecretion that may be observed when treatment with acid-secretory inhibitors is discontinued. Tolerance and rebound related to H2-receptor antagonists has previously been explained as upregulation of gastrin and/or histamine H2-receptors, and/or an increased parietal cell mass. Experimental evidence for these theories is scarce. On the other hand, tolerance can now be explained by a gastrin-induced increase in ECL cell-derived histamine at the parietal cell H2-receptor competing with the antagonist. The lack of tolerance to proton pump inhibitors may be explained by their mode of action, being non-competitive and acting at the H+, K+-ATPase rather than at stimulatory receptors. Post-treatment rebound acid hypersecretion can be understood as gastrin upregulating and/or stimulating growth of the ECL cell, leading to increased amounts of releasable histamine post-treatment. Novel experimental data strongly support this view of the development of tolerance and post-treatment rebound acid hypersecretion.
authors.affiliation: Department of Physiology and Biomedical Engineering, Norwegian University of Science and Technology, Trondheim.
authors.forename: A K
authors.initials: AK
authors.lastname: Sandvik
authors.forename: E
authors.initials: E
authors.lastname: Brenna
authors.forename: H L
authors.initials: HL
authors.lastname: Waldum
mesh_terms: D000818:Animals; D019861:Enterochromaffin-like Cells / Q000187:drug effects*; D005744:Gastric Acid / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D006636:Histamine Release; D006801:Humans; D054328:Proton Pump Inhibitors; D012636:Secretory Rate / Q000187:drug effects
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors