A continuous assessment of ingested food in the gastric lumen is essential for fine-tuning the digestive activities, including the secretion of the regulatory hormones such as gastrin. It has been proposed that G-cells may be able to sense the amount of ingested proteins and adjust the secretion of gastrin accordingly. Our previous studies have shown that G-cells express suitable receptor types, most notably the peptone-receptor GPR92 and the amino acid receptors GPRC6A and CaSR; however, their relative importance remained unclear. To determine the relative quantity of each receptor type, individual G-cells isolated from the transgenic mouse line mGas-EGFP were analyzed by means of a Liquid Chromatography Tandem-Mass Spectrometry (LC-MS/MS) procedure. The results indicate that the relative amount of receptor protein for GPR92 was much higher than for the receptor types GPRC6A and CaSR. These findings support the notion that the peptone-receptor GPR92 may be particularly relevant for sensing partially digested protein products. This view was supported by the finding that a high-protein diet affected the expression level of the peptone-receptor GPR92 in the gastric antrum as well as in the circumvallate papillae.

Gastrin-releasing enteroendocrine cells (G-cells) are usually described as flask-shaped cells with a large base and a small apical pole, integrated in the epithelium lining the basal region of the antral invaginations in the stomach. By means of a transgenic mouse line in which the enhanced version of GFP is endogenously expressed under the control of a gastrin promoter, we have analyzed the spatial distribution and morphological features of G-cells. We found that G-cells were not only located at the basal region of the invagination but to a lesser extent also at the upper region. Visualization of the entire cellular morphology revealed that G-cells show complex morphologies. Basally located G-cells are roundish-shaped cells which project a prominent apical process towards the lumen and extend basal protrusions containing the hormone gastrin that were frequently found in close proximity to blood vessels and occasionally in the vicinity of nerve fibers. Inspection of G-cells in the upper region of antral invaginations disclosed a novel population of G-cells. These cells have a spindle-like contour and long apical and basal processes which extend vertically along the antral invagination, parallel to the lumen. This G-cell population seems to be in contact with a network of nerve fibers. While the functional role of these untypical G-cells is still elusive, the results of this study provide some useful indications to possible roles of these G-cells.