Luminal N alpha-methyl histamine stimulates gastric acid secretion in duodenal ulcer patients via releasing gastrin

Citation
Pc. Konturek et al., Luminal N alpha-methyl histamine stimulates gastric acid secretion in duodenal ulcer patients via releasing gastrin, EUR J PHARM, 412(2), 2001, pp. 181-185
Citations number
19
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN journal
0014-2999 → ACNP
Volume
412
Issue
2
Year of publication
2001
Pages
181 - 185
Database
ISI
SICI code
0014-2999(20010126)412:2<181:LNAHSG>2.0.ZU;2-7
Abstract
N alpha -methyl histamine is an unusual histamine metabolite which is produ ced in the stomach infected by Helicobacter pylori and which was shown in a nimals to stimulate gastric acid secretion and to release gastrin in vitro isolated G-cells, but no information is available regarding its influence o n gastric secretion and gastrin release in duodenal ulcer patients before a nd after H. pylori eradication. In this study, we compared the effects of i ntragastric administration of single or graded doses of N alpha -methyl his tamine on gastric acid secretion and plasma gastrin levels in 16 male duode nal ulcer patients (aging from 35 to 48 years and weighing 65-82 kg) before and after the eradication of H. pylori. Furthermore, the gastric luminal h istamine and gastrin contents were determined before and after H. pylori er adication. In H. pylori-infected duodenal ulcer patients, the intragastric application of N alpha -methyl histamine failed to affect gastric acid secr etion or plasma gastrin levels. Following eradication of H. pylori, gastric luminal histamine and gastrin, and both basal gastric acid secretion and p lasma gastrin levels, were significantly reduced. N alpha -methyl histamine given intragastrically in graded doses to such H. pylori-eradicated duoden al ulcer patients was found to increase dose-dependently gastric acid outpu t reaching at a dose of 5 mg, about 80% of histamine maximum induced by i.v . infusion of 25 mug/kg h of histamine dihydrochloride. We conclude that N alpha -methyl histamine is a potent luminally active stimulant of gastrin r elease and gastric acid secretion in H. pylori-eradicated patients when lum inal histamine is low but is not effective in H. pylori infected patients w hen luminal histamine is enhanced, possibly due to desensitization of gastr in (G-cells) and acid-producing (parietal) cells by No alpha -methyl histam ine produced excessively in H, pylori-infected stomach. (C) 2001 Published by Elsevier Science B.V.