title: Parietal cell activation by arborization of ECL cell cytoplasmic projections is likely the mechanism for histamine induced secretion of hydrochloric acid.
abstract: OBJECTIVE
  Enterochromaffin-like (ECL) cells are central in the regulation of acid secretion. G cells release gastrin and activate ECL cell histamine secretion which stimulates parietal cell H(2) receptors initiating acid secretion. It is unclear whether histamine-mediated parietal cell activation is via a vascular or paracrine pathway. To assess this, we utilized immunohistochemistry (IHC) and electron microscopy to examine gastric tissue and used visualization of formalin fixed dispersed gastric cells and glands to investigate and define the anatomical relationship between ECL and parietal cells.
  
  
  METHODS
  Sprague-Dawley rat stomachs were instilled with formalin. Thereafter fixed mucosal cells and whole gastric glands were dispersed by mechanical and chemical dissolution and enzymatic digestion. Smears with fixed isolated cells and whole glands were stained by IHC with histidine decarboxylase (HDC) and H+/K+-ATPase antibodies. Whole tissue samples of Sprague-Dawley and cotton rat oxyntic mucosa were investigated with IHC using HDC, VMAT2 and H+/K+-ATPase antibodies, and electron microscopy was performed to further delineate the precise anatomic relationship between ECL cells and parietal cells.
  
  
  RESULTS
  Each ECL cell generated a network of HDC- and VMAT2-positive dendritic-like elongations that were in direct contact with several parietal cells. Thus, ECL cells at the base of the gland were in communication with parietal cells in the middle of the gland. Electron microscopy confirmed that the cytoplasmic ECL cell elongations containing secretory vesicles were in direct juxtaposition to parietal cells.
  
  
  CONCLUSIONS
  These findings indicate that ECL cells directly regulate parietal cell function in a neurocrine manner via slender neuron-like elongations.
authors.affiliation: Department of Gastroenterology, St Olavs Hospital HF, Trondheim University Hospital, Trondheim, Norway. bjorn.gustafsson@ntnu.no
authors.forename: Björn I
authors.initials: BI
authors.lastname: Gustafsson
authors.forename: Ingunn
authors.initials: I
authors.lastname: Bakke
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Hauso
authors.forename: Mark
authors.initials: M
authors.lastname: Kidd
authors.forename: Irvin M
authors.initials: IM
authors.lastname: Modlin
authors.forename: Reidar
authors.initials: R
authors.lastname: Fossmark
authors.forename: Eiliv
authors.initials: E
authors.lastname: Brenna
authors.forename: Helge L
authors.initials: HL
authors.lastname: Waldum
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D019861:Enterochromaffin-like Cells / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000033:anatomy & histology* / Q000378:metabolism; D006636:Histamine Release / Q000502:physiology; D007365:Intercellular Junctions / Q000502:physiology; D010295:Parietal Cells, Gastric / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016205:Sigmodontinae