Analysis of the protein related receptor GPR92 in G-cells

Abstract

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.

Nutrient‐sensing components of the mouse stomach and the gastric ghrelin cell

“…GPR93 is a peptone receptor expressed along the GI tract 4,15,74 ; however, limited information is available about the expression of GPR93 in the stomach. 75,76 In the current study, GPR93 had antral-predominant mRNA expression, while GPR93-immunopositive cells were restricted to the antrum. The absence of GPR93-positive cells in the corpus emphasizes the regional expression of this receptor in the stomach and may result from multiple processes, 77 such as post-transcriptional and post-translational regulation, that may inhibit the protein expression of GPR93.…”

“…GPR93 is a peptone receptor expressed along the GI tract 4,15,74 ; however, limited information is available about the expression of GPR93 in the stomach 75,76 . In the current study, GPR93 had antral‐predominant mRNA expression, while GPR93‐immunopositive cells were restricted to the antrum.…”

“…The absence of GPR93-positive cells in the corpus emphasizes the regional expression of this receptor in the stomach and may result from multiple processes, 77 such as post-transcriptional and post-translational regulation, that may inhibit the protein expression of GPR93. In addition, previous studies have shown the expression of this nutrient chemosensor in the antral gastrin 75,76 and somatostatin cells. 76,78 The current study extends this further and demonstrates that GPR93 is highly co-localized with ghrelin, raising the possibility of the involvement of this receptor in the modulation of ghrelin secretion.…”

The Physiology of the Gastric Parietal Cell

“…G34 has a longer half-life and causes long-lasting acid stimulation ( 410 ), suggesting that the processing mechanism can regulate gastrin efficacy. Several G q -coupled receptors for digested protein (peptone and amino acids) are found in G cells, such as CaSR, GPCR6A, and LPAR5 ( 102 , 144 , 309 , 311 ). These chemical sensors are likely a mechanism of amino acid-induced gastrin secretion, subsequently stimulating acid secretion from parietal cells ( 100 ).…”

Review: Chemosensing of nutrients and non-nutrients in the human and porcine gastrointestinal tract

“…In the GIT, the stimulation of the umami heterodimer and the CaSR have been associated with the secretion of CCK, ghrelin and GLP-1 (Liou et al, 2011a;Diakogiannaki et al, 2013;Vancleef et al, 2015). In addition, GPR92/93 has been reported in stomach G-cells and STC-1 cells responding to a protein hydrolysate by releasing CCK (Choi et al, 2007;Rettenberger et al, 2015).…”