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1 Pathology & Laboratory Medicine, UCLA, Los Angeles, CA, USA; Physiology, UCLA, Los Angeles, CA, USA; Membrane Biology Laboratory, West Los Angeles Veterans Affairs Medical Center, Los Angeles, CA, USA
2 Physiology, UCLA, Los Angeles, CA, USA; Membrane Biology Laboratory, West Los Angeles Veterans Affairs Medical Center, Los Angeles, CA, USA
3 Physiology, UCLA, Los Angeles, CA, USA; Medicine, UCLA, Los Angeles, CA, USA; Membrane Biology Laboratory, West Los Angeles Veterans Affairs Medical Center, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: nilslam{at}ucla.edu.
The gastric enterochromaffin-like (ECL) cell plays a key regulatory role in peripheral regulation of acid secretion due to the release of histamine that stimulates acid secretion by the parietal cell. Studies in intact animals, gastric glands and isolated cells after short term culture have shown expression of stimulatory CCK-2 and PAC-1 and inhibitory SST-2 and Gal1 receptors as well as histidine decarboxylase. However, the pattern of its gene expression as a neuroendocrine cell has not been explored. Comparison of gene expression by 95% pure ECL cells obtained by density gradient, elutriation and FACS sorting with isolates of the intact fundic gastric epithelium (i.e. "subtractive hybridization") identified a variety of additional expressed gene families characteristic of this neuroendocrine cell. These include genes 1) involved in neuropeptide synthesis and secretory vesicle exocytosis, 2) involved in control of inflammation, 3) implicated in healing of the epithelium, 4) encoding inhibitory Gi-protein coupled receptors, 5) playing a role in neuroendocrine regulation of food intake and 6) encoding proteins likely involved in maintenance of circadian rhythm, in addition to the ECL cell specific genes histidine decarboxylase and monoamine transporter. Particularly, the inhibitory apelin receptor gene, APJ, was highly expressed in the ECL cell preparation. Since parietal cells express apelin, immunohistochemical and functional studies showed that there is an inhibitory feed back loop between the parietal and ECL cell during gastrin stimulation, providing evidence for a novel pathway of down regulation of acid secretion due to interaction between these two cell types.
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