Abstract
The gastric X/A-like endocrine cell receives growing attention due to its peptide products with ghrelin being the best characterized. This peptide hormone was identified a decade ago as a stimulator of food intake and to date remains the only known peripherally produced and centrally acting orexigenic hormone. In addition, subsequent studies identified numerous other functions of this peptide including the stimulation of gastrointestinal motility, the maintenance of energy homeostasis and an impact on reproduction. Moreover, ghrelin is also involved in the response to stress and assumed to play a role in coping functions and exert a modulatory action on immune pathways. Our knowledge on the regulation of ghrelin has markedly advanced during the past years by the identification of the ghrelin acylating enzyme, ghrelin-O-acyltransferase, and by the description of changes in expression, activation, and release under different metabolic as well as physically and psychically challenging conditions. However, our insight on regulatory processes of ghrelin at the cellular and subcellular levels is still very limited and warrants further investigation.
Highlights
Several enteroendocrine cells have been identified in the stomach and shown to influence physiological functions with a predominant effect on gastric acid secretion, namely gastrinproducing cells (G cells), somatostatin-releasing cells (D cells, 5–10% of gastric oxyntic endocrine cells in rats, >20% in humans), enterochromaffin-like cells releasing histamine (ECL, 65% in rats, 30% in humans), and much less abundantly the serotonincontaining enterochromaffin (EC) cells (Rindi et al, 2004)
A distinct cell type has been identified in the stomach that is distributed throughout the mucosa (Figure 1) that was termed X/A-like cell in rats and P/dopamine receptor subtype 1 (D1) cell in humans (Date et al, 2000; Mizutani et al, 2009)
Mice lacking neuropeptide Y (NPY) and agouti-related peptide (AgRP) do not respond to peripherally injected ghrelin whereas mice with a single peptide gene knockout still showed an increased food intake giving rise to a compensation of NPY by AgRP and vice versa (Chen et al, 2004). These data along with the expression of ghrelin receptor (GRLN-R) in over 90% of all NPY neurons in the ARC while the GRLN-R is only present in less than 8% of pro-opiomelanocortin (POMC) neurons (Willesen et al, 1999) show that the orexigenic effect of ghrelin is mediated by central AgRP and NPY signaling
Summary
Several enteroendocrine cells have been identified in the stomach and shown to influence physiological functions with a predominant effect on gastric acid secretion, namely gastrinproducing cells (G cells), somatostatin-releasing cells (D cells, 5–10% of gastric oxyntic endocrine cells in rats, >20% in humans), enterochromaffin-like cells releasing histamine (ECL, 65% in rats, 30% in humans), and much less abundantly the serotonincontaining enterochromaffin (EC) cells (Rindi et al, 2004). A distinct cell type has been identified in the stomach that is distributed throughout the mucosa (Figure 1) that was termed X/A-like cell in rats and P/D1 cell in humans (Date et al, 2000; Mizutani et al, 2009). Studies in mice ingesting different concentrations of medium-chain fatty acids (MCFA) or medium-chain triacylglycerols (MCT) established their direct use as a source for ghrelin acyl modification (Nishi et al, 2005) Without this posttranslational modification desacyl ghrelin is obtained which does not bind to the GRLN-R. The gastric endocrine X/A-like cells are www.frontiersin.org
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