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Functional characterization of ghrelin secreting A‐like cells isolated from rat gastric mucosa

Recent reports showed that gastric small endocrine cells, especially A‐like cells, produce orexigenic ghrelin and anorexigenic nesfatin‐1, suggesting the important roles in the regulation of food intake and satiety. However, the mechanisms in the direct regulation of ghrelin and nesfatin‐1 secretion from A‐like cells are still unknown. To clarify these, we established A‐like cell culture isolated from rat stomach using a counterflow elutriation. We successfully enriched A‐like cells from the dispersed gastric mucosal cells confirmed by real‐time RT‐PCR and immunocytochemistry. The cultured cells secreted detectable amounts of ghrelin and nesfatin‐1 in cell culture supernatants. Pharmacological analysis revealed that ghrelin secretion was strongly stimulated by adrenalin via beta receptors, but, not by leptin or endothelin‐1. In contrast, nesfatin‐1 secretion was stimulated by endothelin‐1. These results indicate that ghrelin and nesfain‐1 secretions from gastric A‐like cells were differentially regulated by endogenous substances. Thus, our A‐like cell culture is quite valuable model to clarify the direct regulation of hormone secretions from the cells. This method would help to explore the new therapeutic targets by regulating food intake and satiety via gastric hormones.