[Histamine and its role in peptic gastric diseases: the discovery of histamine-H2-receptor antagonists].
For the definition of histamine receptors the following prerequisites must be fulfilled: (1) Course of dose-response curves according to the mass-action law; (2) parallel displacement of these curves to the right in the presence of antagonists; (3) inhibition only by specific histamine antagonists; (4) slope of a Schild-plot not significantly different from unity. For H2-receptors these prerequisites could ideally be fulfilled, especially by the development of highly specific H2-receptor antagonists. However, this new class of compounds acts not only by mere competitive inhibition of histamine at its H2-receptor, but also by activating the metabolism of this secretagogue. A further explanation of the action of H2-receptor antagonists in the treatment of chronic duodenal ulcer may be given by studying the pathogenetic role played by histamine in the development of this disease: duodenal ulcer patients showed an increased liberation of histamine from mucosal mast cell stores as well as a decreased activity of histamine methyltransferase (i. e. longer action of histamine!). The rise in histamine content and histamine methyltransferase activity after vagotomy may be the basis for a biochemical explanation of the acid-reducing effect of this operation.
D000818:Animals; D002049:Burimamide / Q000138:chemical synthesis; D002415:Cats; D002927:Cimetidine / Q000138:chemical synthesis; D004285:Dogs; D004381:Duodenal Ulcer / Q000209:etiology; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006637:Histamine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D010418:Pentagastrin; D010437:Peptic Ulcer / Q000188:drug therapy*; D051381:Rats; D011970:Receptors, Histamine H2; D014628:Vagotomy
D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006637:Histamine N-Methyltransferase; D010418:Pentagastrin; D002049:Burimamide
Histamin und seine Rolle bei peptischen Magenerkrankungen: Die Entdeckung der Histamin-H2-Rezeptorantagonisten.