title: The mechanism of histamine secretion from gastric enterochromaffin-like cells.
abstract: Enterochromaffin-like (ECL) cells play a pivotal role in the peripheral regulation of gastric acid secretion as they respond to the functionally important gastrointestinal hormones gastrin and somatostatin and neural mediators such as pituitary adenylate cyclase-activating peptide and galanin. Gastrin is the key stimulus of histamine release from ECL cells in vivo and in vitro. Voltage-gated K(+) and Ca(2+) channels have been detected on isolated ECL cells. Exocytosis of histamine following gastrin stimulation and Ca(2+) entry across the plasma membrane is catalyzed by synaptobrevin and synaptosomal-associated protein of 25 kDa, both characterized as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein. Histamine release occurs from different cellular pools: preexisting vacuolar histamine immediately released by Ca(2+) entry or newly synthesized histamine following induction of histidine decarboxylase (HDC) by gastrin stimulation. Histamine is synthesized by cytoplasmic HDC and accumulated in secretory vesicles by proton-histamine countertransport via the vesicular monoamine transporter subtype 2 (VMAT-2). The promoter region of HDC contains Ca(2+)-, cAMP-, and protein kinase C-responsive elements. The gene promoter for VMAT-2, however, lacks TATA boxes but contains regulatory elements for the hormones glucagon and somatostatin. Histamine secretion from ECL cells is thereby under a complex regulation of hormonal signals and can be targeted at several steps during the process of exocytosis.
authors.affiliation: Department of Medicine II, Technical University of Munich, D-81675 Munich, Germany. christine.prinz@lrz.tum.de
authors.forename: C
authors.initials: C
authors.lastname: Prinz
authors.forename: R
authors.initials: R
authors.lastname: Zanner
authors.forename: M
authors.initials: M
authors.lastname: Gerhard
authors.forename: S
authors.initials: S
authors.lastname: Mahr
authors.forename: N
authors.initials: N
authors.lastname: Neumayer
authors.forename: B
authors.initials: B
authors.lastname: Höhne-Zell
authors.forename: M
authors.initials: M
authors.lastname: Gratzl
mesh_terms: D004759:Enterochromaffin Cells / Q000166:cytology / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology* / Q000378:metabolism; D006636:Histamine Release / Q000502:physiology*