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 (PACAP) and galanin. Gastrin increases histamine release by activation of Cholecystokinin (CCK)-B receptors followed by entry of calcium and exocytosis catalyzed by the SNARE proteins SNAP-25 and synaptobrevin. Somatostatin inhibits histamine release by activation of specific subtype 2 receptors and inhibition of calcium entry at the plasma membrane. PACAP stimulates calcium release and entry, cAMP and histamine release, whereas galanin blocks calcium signaling and histamine release. Histamine is synthesized by cytoplasmic histidine decarboxylase (HOC) and accumulated in the secretory vacuoles by proton-histamine countertransport via the vacuolar monoamine transporter (VMAT) subtype 2. The promoter region of HOC contains calcium-, cAMP- and protein kinase C-responsive elements. The gene promoter for VMAT-2, however, lacks calcium-responsive sites and TATA-boxes but contains regulatory elements for the hormones glucagon and somatostatin. Exocytosis of histamine occurs from different cellular pools, pre-existing vacuolar histamine immediately released by calcium entry or the newly synthesized histamine following gastrin induction of HOC. Histamine secretion from ECL cells is under a complex regulation of hormonal signals and can be targeted at several steps during the process of exocytosis.
| Original language | English |
|---|---|
| Pages (from-to) | 1090 |
| Number of pages | 1 |
| Journal | Zeitschrift fur Gastroenterologie |
| Volume | 36 |
| Issue number | 12 |
| State | Published - 1998 |