Adrenergic and Cromolyn Sodium Modulation of ECL Cell Histamine Secretion

Abstract

The histamine secreting enterochromaffin-like (ECL) cell is now recognized as the principal regulator of gastric acid secretion. Histamine is not only a primary modulator of acid secretion, but may be of relevance in gastritis and as a mitogen in gastric neoplasia. Study of the ECL cell has been limited since no pure preparation was available. We therefore developed a pure isolated ECL cell preparation with a purity of 90-95% as determined by total histamine content and chromogranin immunofluorescence. Trypan blue exclusion demonstrated >95% viability. While gastrin and acetylcholine are known modulators of acid secretion, the role of adrenergic neurotransmitters has not been clearly delineated. The purpose of this study was to examine adrenergic modulation of ECL cell histamine release. To further define the inhibitory mechanisms of histamine secretion, we evaluated the mast cell histamine inhibitor sodium cromoglycate. Histamine secretion was determined by radioimmunoassay. Basal secretion was 0.6 ± 0.2 nmol/103 cells. Gastrin stimulated histamine secretion with an EC50 of 3 × 10-10M . Octopamine (α-adrenergic agonist) (10-11-10-4M) failed to stimulate histamine secretion. Isoproterenol (β-adrenergic agonist) stimulated histamine secretion (EC50, 6 × 10-8M) and was inhibited by propranolol (IC50 5 × 10-10M). Sodium cromoglycate inhibited isoproterenol (IC50 10-7M ) and gastrin (IC50 10-8M), and forskolin stimulated histamine secretion (IC50 10-7M). Isoproterenol resulted in an increase of ECL cell cAMP which was not inhibited by sodium cromoglycate. These data are consistent with the presence of a β-adrenergic, but not an αadrenergic, receptor on the ECL cell and suggests a role of the adrenergic neural system in the modulation of ECL cell function. The effect of the mast cell histamine release inhibitor suggests a common mechanism for histamine release by both mast cells and ECL cells.