Ghrelin - a pleiotropic hormone secreted from endocrine x/a-like cells of the stomach

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.

Keywords: GOAT; NUCB2; acyl and desacyl; endocrine cells; ghrelin; nesfatin-1; stress.

Figure 1

Immunohistochemical photomicrograph of X/A-like cells in the rat gastric oxyntic mucosa of ad libitum fed male rats. Ghrelin-positive X/A-like cells (arrows) are evenly distributed throughout the entire length of the gastric oxyntic glands. The scale bar represents 50 μm.

Figure 2

Somatostatin could act directly on gastric X/A-like cells by interaction with the somatostatin receptor subtype 2 (sst₂) localized on these cells. (A,B) Ghrelin-positive X/A-like cells in the gastric oxyntic mucosa express the sst_2a receptor in naive rats. Paraffin-embedded gastric corpus sections of ad libitum fed rats were processed for immunofluorescent double labeling. Confocal microscopy shows the localization of sst_2a-immunopositive cells throughout the gastric oxyntic mucosa [(A), red], whereas ghrelin-positive cells are localized mostly in the middle and the lower part of the glands [(A), green]. The higher magnification (B) shows that ghrelin-positive cells express the sst_2a receptor (arrow). Lu, lumen; Mu, mucosa; Submu, submucosa. (C,D) The sst₂ agonist decreases circulating acyl and desacyl ghrelin levels in overnight-fasted rats implanted with an intrajugular catheter. The sst₂ agonist (100 μg/rat in 200 μl saline containing 0.1% BSA) or vehicle (saline containing 0.1% BSA) was injected intravenously (iv) twice at 0 and 0.5 h. Blood was withdrawn before the second injection at 0.5 and at 2 h and processed for acyl (A) and total ghrelin measurement. Desacyl ghrelin (B) was calculated as the difference of total minus acyl ghrelin for each individual sample. Each bar represents the means ± SEM of number of rats indicated at the bottom of the column. *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle. Reproduced with permission from reference (Stengel et al., 2011b).

Figure 3

Schematic overview of ghrelin derived from gastric X/A-like cells or immune cells and effect on cytokine production and release from immune cells under immune challenge conditions.