Secretory organelles in ECL cells: Effects of pharmacological blockade of the gastrin/CCK2 receptor versus its elimination by gene targeting

Histamine-producing ECL cells are numerous in the stomach. They express gastrin/CCK₂ receptors and respond to gastrin by releasing histamine. Ultrastructurally, they display numerous and very characteristic secretory organelles: granules, secretory vesicles and microvesicles. This paper focuses on the impact of the gastrin/CCK₂ receptor on the ultrastructure of the ECL cells. The effects of pharmacological blockade of the receptor are compared with the effects of receptor elimination following selective gene targeting. Long-term administration of powerful gastrin/CCK₂ receptor antagonists was found to induce hypotrophy of rat stomach ECL cells with reduced number of granules, secretory vesicles and microvesicles. In gastrin/CCK₂ receptor knockout mice ECL cells, i.e., histamine-storing cells with the characteristic ultrastructure of ECL cells, had disappeared from the oxyntic mucosa and been replaced by a novel population of endocrine-like cells. These cells harbored granules and microvesicles, but were devoid of histamine and secretory vesicles. We suggest that the gastrin/CCK₂ receptor is important for the proper differentiation of the ECL cells and for maintaining their characteristic ultrastructure.