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Abstract
Monitoring the luminal content in the stomach is of vital importance for adjusting the gastric activities, including the release of gastric hormones such as gastrin. Our previous studies have shown that in mice the gastrin-secreting G-cells express receptor types which are responsive to amino acids. Since the pig is considered as more suitable model for studying gastro-physiological aspects relevant for men, in this study we have analyzed the distribution of G-cells and D-cells in the gastric antrum of men, swine, and mouse and the expression of receptor types which may render these cells responsiveness to protein breakdown products. The results indicate that the number of G-cells per antral invagination was significantly higher in swine and human compared to mice and also the distribution pattern of G-cells differed between the species. The molecular phenotyping revealed that the receptors GPRC6A and CaSR were also expressed in G-cells and in a subpopulation of D-cells from swine and men. As an additional receptor type, the peptone-receptor GPR92, was found to be expressed in G-cells and a subpopulation of D-cells; this receptor type may be particular suitable for sensing protein breakdown products and thus be a key element to adjust the activity of G-cells and D-cells according to the progress of the digestive processes in the stomach. In search for elements of an intracellular signaling cascade it was found that G-cells express the G-protein subunit Gαq as well as the phospholipase C subtype PLCβ3; in contrast, D-cells expressed the subtype PLCβ2 and neither Gαq. These results indicate that there are significant species differences concerning the number and distribution pattern, but not concerning the molecular phenotype of the gastric endocrine cells. However, G-cells and D-cells significantly differ from each other regarding the repertoire of receptors and signaling elements.
Highlights
Physiological processes in the gastrointestinal tract, such as motility, acid secretion, and the release of hormones must permanently be adjusted according to the composition of ingested food
In order to establish a solid basis for comparing number and distribution of distinct gastric cell types in the stomach of mouse, www.frontiersin.org swine, and human we initially set out to investigate some structural features of the antral mucosa
In human specimen the G-protein coupled receptor class C member 6A (GPRC6A) immunoreactivity was most intense at the apical part of cells contacting the central lumen, whereas gastrin immunoreactivity was predominantly found at the base of cells
Summary
Physiological processes in the gastrointestinal tract, such as motility, acid secretion, and the release of hormones must permanently be adjusted according to the composition of ingested food. In the stomach, sensing of protein breakdown products is of particular significance as they activate antral G-cells which release gastrin, the central hormone for controlling gastric activities (Zeng et al, 1995; Dockray et al, 2001, 2005). The activity of G-cells is negatively controlled by somatostatin which is released from antral D-cells. It is essential for both cell types to fine-tune their activities according to the amount of proteins and their breakdown products in the luminal content of the stomach. Previous studies have demonstrated that in mice the endocrine G-cells and D-cells express receptor types which are responsive to amino acids
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