Am J Physiol Cell Physiol AJP: Gastrointestinal and Liver Physiology
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Am J Physiol Cell Physiol 277: C845-C855, 1999;
0363-6143/99 $5.00
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Vol. 277, Issue 5, C845-C855, November 1999

INVITED REVIEW
The mechanism of histamine secretion from gastric enterochromaffin-like cells

Christian Prinz1, Robert Zanner1, Markus Gerhard1, Sabine Mahr1, Nina Neumayer1, Barbara Höhne-Zell2, and Manfred Gratzl2

Departments of 1 Medicine II and 2 Anatomy, Technical University of Munich, D-81675 Munich, Germany

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 Ca2+ channels have been detected on isolated ECL cells. Exocytosis of histamine following gastrin stimulation and Ca2+ 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 Ca2+ 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 Ca2+-, 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.

histidine decarboxylase; exocytosis; neuroendocrine; high-voltage-activated calcium channels; vesicular monoamine transporter


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