Abstract
Taste receptors on enteroendocrine cells sense nutrients and transmit signals that control gut hormone release. This study aimed to investigate the amino acid (AA) sensing mechanisms of the ghrelin cell in a gastric ghrelinoma cell line, tissue segments and mice. Peptone and specific classes of amino acids stimulate ghrelin secretion in the ghrelinoma cell line. Sensing of L-Phe occurs via the CaSR, monosodium glutamate via the TAS1R1-TAS1R3 while L-Ala and peptone act via 2 different amino acid taste receptors: CaSR & TAS1R1-TAS1R3 and CaSR & GPRC6A, respectively. The stimulatory effect of peptone on ghrelin release was mimicked ex vivo in gastric but not in jejunal tissue segments, where peptone inhibited ghrelin release. The latter effect could not be blocked by receptor antagonists for CCK, GLP-1 or somatostatin. In vivo, plasma ghrelin levels were reduced both upon intragastric (peptone or L-Phe) or intravenous (L-Phe) administration, indicating that AA- sensing is not polarized and is due to inhibition of ghrelin release from the stomach or duodenum respectively. In conclusion, functional AA taste receptors regulate AA-induced ghrelin release in vitro. The effects differ between stomach and jejunum but these local nutrient sensing mechanisms are overruled in vivo by indirect mechanisms inhibiting ghrelin release.
Highlights
The chemosensory signalling pathways involved in sensing of peptides and amino acids by the ghrelin cell are unknown
Since ghrelin cells exist as closed-type cells in the stomach, not reaching the epithelial surface, or opened-type cells in the small intestine, making contact to the lumen, we investigated whether the effect of peptone on ghrelin release differed in ex vivo segments from corpus and jejunum[31]
Our findings in the ghrelinoma cell line MGN3-1 provide for the first time evidence that peptone, umami and specific classes of amino acids are sensed by amino acid taste receptors (CaSR, GPRC6A, TAS1R1-TAS1R3 or a combination) on the gastric ghrelin cell and stimulate octanoyl ghrelin release
Summary
The chemosensory signalling pathways involved in sensing of peptides and amino acids by the ghrelin cell are unknown. Studies in Pept1−/− mice showed that PepT1 participates in the control of food intake in mice fed a high-protein diet[28] These data suggest that sensing of amino acids and protein hydrolysates by endocrine cells in the gut is finely tuned by different receptors and transporters that may play an important role in protein-induced satiety. Recent studies showed that the ghrelin cell expresses TAS1R3, involved in sensing of sweet and umami, and the free fatty acid receptor GPR120 and the gustatory G-proteins, α -gustducin and α -transducin, coupled to several taste receptors[23,29,30]. This study aimed to examine the role of specific amino acid taste receptors in the effect of peptone, a casein hydrolysate rich in peptides and amino acids, and individual amino acids on ghrelin release in the ghrelinoma cell line. We examined whether amino acids are sensed via the lumen or bloodstream by comparing the effect of intragastric versus intravenous administration of peptone or L-Phe on ghrelin release in mice
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