Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa.

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.