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Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa
F Schmitz1, M N Göke, J M Otte
1Department of Medicine I, St. Josef-Hospital, Ruhr-University of Bochum, D-44791, Bochum, Germany. frank.schmitz@uni-bochum.de
Abstract:
Gastrin stimulates gastric acid secretion in various species, but the role of the structurally related CCK for the peripheral regulation of acid secretion in humans remains controversial. Moreover, species differences in CCK receptor function and expression have been reported. We therefore sought to identify the cellular targets of CCK and gastrin within the human gastric mucosa in situ. Gastric biopsies were collected from 15 patients without gastric disease. Expression of CCK receptor subtypes was detected in individual cells of the gastric mucosa by reverse transcription (RT)-PCR in situ, immunohistochemistry and confocal laser scanning microscopy, using antisera against the CCK-A or CCK-B/gastrin receptor subtype. Both CCK-A and CCK-B receptors were detected in antral and oxyntic mucosa at the mRNA and protein level. In fundic mucosa, CCK-A receptor mRNA and protein mapped to D cells (37.4+/-7.7). Besides, individual chief cells, mucous neck cells and parietal cells (12.3+/-4.7%) expressed CCK-A receptors. CCK-B/gastrin receptor mRNA and protein were detected in parietal cells (57.4+/-11.1%) and in neuroendocrine cells (33.2+/-4.4%) expressing chromogranin A. Furthermore, epithelial cells within the neck of the gastric gland were found to express the CCK-B/gastrin receptor. We conclude that (i) identification of CCK-A receptors on somatostatin producing D cells in humans provide the anatomical basis for a receptor-mediated mode of action of CCK on somatostatin release and (ii) detection of either CCK receptor subtype in the putative stem cell compartment implies a role of CCK in the maintenance of tissue homeostasis in human gastric mucosa.
Insights
Cholecystokinin (CCK) and gastrin receptors are found in human stomach cells, including those regulating acid and somatostatin secretion. This suggests CCK plays a role in maintaining stomach tissue health.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cell Biology
Background:
- Gastrin stimulates gastric acid secretion, but the role of cholecystokinin (CCK) in human gastric acid regulation is debated.
- Species-specific differences in CCK receptor function and expression are known.
Purpose of the Study:
- To identify the specific cells in the human gastric mucosa that express CCK and gastrin receptors.
- To elucidate the cellular targets of CCK and gastrin in the human stomach.
Main Methods:
- Gastric biopsies from 15 healthy individuals were analyzed.
- Reverse transcription (RT)-PCR in situ, immunohistochemistry, and confocal laser scanning microscopy were used.
- Detection of CCK-A and CCK-B/gastrin receptor subtypes at mRNA and protein levels.
Main Results:
- Both CCK-A and CCK-B/gastrin receptors were found in antral and oxyntic mucosa.
- CCK-A receptors were located on D cells (producing somatostatin), chief cells, mucous neck cells, and parietal cells in the fundic mucosa.
- CCK-B/gastrin receptors were identified in parietal cells, neuroendocrine cells (chromogranin A-positive), and epithelial cells in the gastric gland neck.
Conclusions:
- CCK-A receptors on human D cells provide a basis for CCK's action on somatostatin release.
- The presence of CCK receptor subtypes in the gastric stem cell compartment suggests a role for CCK in human gastric mucosa homeostasis.
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