The mechanism of histamine secretion from gastric enterochromaffin-like cells

Enterochromaffin-like (ECL) cells play a pivotal role in the peripheral reg ulation of gastric acid secretion as they respond to the functionally impor tant gastrointestinal hormones gastrin and somatostatin and neural mediator s such as pituitary adenylate cyclase-activating peptide and galanin. Gastr in is the key stimulus of histamine release from ECL cells in vivo and in v itro. Voltage-gated K-divided by and Ca-2 divided by channels have been det ected on isolated ECL cells. Exocytosis of histamine following gastrin stim ulation and Ca-2 divided by entry across the plasma membrane is catalyzed b y synaptobrevin and synaptosomal-associated protein of 25 kDa, both charact erized as a soluble N-ethylmaleimide-sensitive factor attachment protein re ceptor protein. Histamine release occurs from different cellular pools: pre existing vacuolar histamine immediately released by Ca2+ entry or newly syn thesized histamine following induction of histidine decarboxylase (HDC) by gastrin stimulation. Histamine is synthesized by cytoplasmic HDC and accumu lated in secretory vesicles by proton-histamine countertransport via the ve sicular monoamine transporter subtype 2 (VMAT-2). The promoter region of HD C contains Ca2+ -, cAMP-, and protein kinase C-responsive elements. The gen e promoter for VMAT-2, however, lacks TATA boxes but contains regulatory el ements for the hormones glucagon and somatostatin. Histamine secretion from ECL cells is thereby under a complex regulation of:hormonal signals and ca n be targeted at several steps during the process of exocytosis.