CCK2 receptors are necessary for the differentiation and proliferation of ECL cells in mouse and rat stomach

Abstract

ECL cells in the oxyntic mucosa of the mouse and rat stomach express CCK2 receptors, which enable them to respond to gastrin by the production and release of histamine. We have studied CCK2 receptor-deficient mice and rats subjected to pharmacological CCK2 receptor blockade in an attempt to demonstrate the importance of gastrin signaling for ECL-cell differentiation and proliferation. In CCK2 receptor knockout mice, the ECL cells were replaced by a novel endocrine-like cell type lacking histamine and histidine decarboxylase but retaining pancreastatin and vesicle monoamine transporter type 2 (VMAT2). Ultrastructurally, they were characterized by the presence of small dense-core granules and microvesicles and by the absence of the secretory vesicles that are a hallmark feature of wild-type ECL cells. Upon pharmacological CCK2 receptor blockade, the ECL cells became small and inactive, although unchanged in number. By immunocytochemistry (histamine, pancreastatin and VMAT2) and electron microscopy (secretory vesicles) they remained recognizable as ECL cells; their proliferation in response to hypergastrinemia was prevented.