title: Gastric acid secretion in L-histidine decarboxylase-deficient mice.
abstract: OBJECTIVE
  Histamine, gastrin, and acetylcholine are known to be the primary secretagogues of gastric acid secretion, but how the roles are shared among these secretagogues remains to be fully clarified. To evaluate the cooperation between histamine and the other secretagogues, acid secretion responses induced by each secretagogue were measured in L-histidine decarboxylase (HDC)-deficient mice.
  
  
  METHODS
  Acid secretion was measured by the titration of acid under anesthesia. The expression of selected genes involved in acid secretion was determined by Northern blot and/or immunoblot analysis. Histamine-2 (H(2)) receptor binding in the gastric mucosa was investigated using [(3)H]tiotidine.
  
  
  RESULTS
  HDC-deficient mice showed low basal and high exogenous histamine-stimulated acid secretion. The mutant mice showed hypergastrinemia and did not undergo acid secretion upon treatment with exogenous gastrin. However, carbachol stimulated weak and transient acid secretion in the mutants. The Bmax values for H(2) and the expression of Gs alpha in gastric mucosal membranes were higher in the mutants than in the wild-type mice.
  
  
  CONCLUSIONS
  This study confirms the concept that histamine production is essential for gastric acid secretion induced by gastrin, but not for that induced by carbachol. HDC-deficient mice should be a suitable model for further functional analyses of the correlation between histamine and the other acid secretagogues.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kiyoma
authors.initials: K
authors.lastname: Hamada
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamada
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sugita
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tonai
authors.forename: Bèla
authors.initials: B
authors.lastname: Hunyady
authors.forename: Miklòs
authors.initials: M
authors.lastname: Palkovits
authors.forename: Andras
authors.initials: A
authors.lastname: Falus
authors.forename: Takehiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Susumu
authors.initials: S
authors.lastname: Okabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ichikawa
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics*; D006727:Hormone Antagonists / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D010276:Parasympatholytics / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000235:genetics; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism
chemical_list: D001570:Benzodiazepinones; D018679:Cholinergic Agonists; D005755:Gastrins; D006727:Hormone Antagonists; D010276:Parasympatholytics; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D011970:Receptors, Histamine H2; D001285:Atropine; D006632:Histamine; D002217:Carbachol; D006640:Histidine Decarboxylase; C104428:YF 476