title: Dual inhibitory pathways link antral somatostatin and histamine secretion in human, dog, and rat stomach.
abstract: OBJECTIVE
  The secretion and function of antral histamine are not known. The aims of this study were to characterize the mechanisms of histamine release from the gastric antrum of humans, dogs, and rats and to determine whether histamine can influence the secretion of somatostatin and gastrin.
  
  
  METHODS
  Somatostatin, gastrin, and histamine secretion from superfused antral segments was measured using radioimmunoassay.
  
  
  RESULTS
  Superfusion with thioperamide (H3 antagonist) increased somatostatin and decreased gastrin and histamine secretion in all three species; superfusion with (r)-alpha-methylhistamine (H3 agonist) had the opposite effect. The pattern implied that endogenous histamine, acting via H3 receptors, exerts an inhibitory paracrine influence on somatostatin secretion, which in turn regulates gastrin secretion. Superfusion with somatostatin antibody increased histamine secretion; the increase was not affected by the gastrin antagonist L-365,260, implying that it was not mediated by the concurrent increase in gastrin but by suppression of an inhibitory pathway linking somatostatin and histamine. Superfusion with methacholine alone and in the presence of either the H3 agonist or antagonist confirmed the existence of reciprocal inhibitory pathways linking somatostatin and histamine.
  
  
  CONCLUSIONS
  Antral histamine in humans, dogs, and rats is linked to antral somatostatin via reciprocal inhibitory paracrine pathways that serve to amplify the regulatory influence of somatostatin.
authors.affiliation: Department of Medicine, Medical College of Virginia, Richmond, USA.
authors.forename: L
authors.initials: L
authors.lastname: Vuyyuru
authors.forename: M L
authors.initials: ML
authors.lastname: Schubert
authors.forename: L
authors.initials: L
authors.lastname: Harrington
authors.forename: A
authors.initials: A
authors.lastname: Arimura
authors.forename: G M
authors.initials: GM
authors.lastname: Makhlouf
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D004285:Dogs; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology; D008761:Methylhistamines / Q000494:pharmacology; D009434:Neural Pathways / Q000502:physiology; D010671:Phenylurea Compounds; D010880:Piperidines / Q000494:pharmacology; D011706:Pyloric Antrum / Q000378:metabolism*; D051381:Rats; D013004:Somatostatin / Q000378:metabolism* / Q000502:physiology
chemical_list: D001570:Benzodiazepinones; D005755:Gastrins; D006633:Histamine Antagonists; D008761:Methylhistamines; D010671:Phenylurea Compounds; D010880:Piperidines; D016210:Methacholine Chloride; C058121:L 365260; D013004:Somatostatin; C052075:thioperamide