Endocrinology (Philadelphia), 2013-10, Vol.154 (10), p.3552-3564
2013
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Details
- Autor(en) / Beteiligte
- Titel
- GPR41/FFAR3 and GPR43/FFAR2 as Cosensors for Short-Chain Fatty Acids in Enteroendocrine Cells vs FFAR3 in Enteric Neurons and FFAR2 in Enteric Leukocytes
- Ist Teil von
- Endocrinology (Philadelphia), 2013-10, Vol.154 (10), p.3552-3564
- Ort / Verlag
- Chevy Chase, MD: Endocrine Society
- Erscheinungsjahr
- 2013
- Quelle
- Oxford Journals 2020 Medicine
- Beschreibungen/Notizen
- The expression of short-chain fatty acid receptors GPR41/FFAR3 and GPR43/ free fatty acid receptor 2 (FFAR2) was studied in the gastrointestinal tract of transgenic monomeric red fluorescent protein (mRFP) reporter mice. In the stomach free fatty acid receptor 3 (FFAR3)-mRFP was expressed in a subpopulation of ghrelin and gastrin cells. In contrast, strong expression of FFAR3-mRFP was observed in all cholecystokinin, glucose-dependent insulinotropic peptide (GIP), and secretin cells of the proximal small intestine and in all glucagon-like peptide-1 (GLP-1), peptide YY, and neurotensin cells of the distal small intestine. Throughout the colon and rectum, FFAR3-mRFP was strongly expressed in the large population of peptide YY and GLP-1 cells and in the neurotensin cells of the proximal colon. A gradient of expression of FFAR3-mRFP was observed in the somatostatin cells from less than 5% in the stomach to more than 95% in the rectum. Substance P-containing enterochromaffin cells displayed a similar gradient of FFAR3-mRFP expression throughout the small intestine. Surprisingly, FFAR3-mRFP was also expressed in the neuronal cells of the submucosal and myenteric ganglia. Quantitative PCR analysis of fluorescence-activated cell sorting (FACS) purified FFAR3-mRFP positive cells confirmed the coexpression with the various peptide hormones as well as key neuronal marker proteins. The FFAR2-mRFP reporter was strongly expressed in a large population of leukocytes in the lamina propria of in particular the small intestine but surprisingly only weakly in a subpopulation of enteroendocrine cells. Nevertheless, synthetic ligands specific for either FFAR3 or FFAR2 each released GLP-1 from colonic crypt cultures and the FFAR2 agonist mobilized intracellular Ca2+ in FFAR2 positive enteroendocrine cells. It is concluded that FFAR3-mRFP serves as a useful marker for the majority of enteroendocrine cells of the small and large intestine and that FFAR3 and FFAR2 both act as sensors for short-chain fatty acids in enteroendocrine cells, whereas FFAR3 apparently has this role alone in enteric neurons and FFAR2 in enteric leukocytes.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0013-7227eISSN: 1945-7170DOI: 10.1210/en.2013-1142Titel-ID: cdi_proquest_miscellaneous_1435844442
- Format
- –
- Schlagworte
- Animals, Biological and medical sciences, Biomarkers - metabolism, Cells, Cultured, Enteric Nervous System - metabolism, Enteroendocrine Cells - cytology, Enteroendocrine Cells - metabolism, Fatty Acids, Volatile - metabolism, Fundamental and applied biological sciences. Psychology, Gastrointestinal Tract - cytology, Gastrointestinal Tract - immunology, Gastrointestinal Tract - innervation, Gastrointestinal Tract - metabolism, Genes, Reporter, Leukocytes - immunology, Leukocytes - metabolism, Ligands, Luminescent Proteins - genetics, Luminescent Proteins - metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mucous Membrane - cytology, Mucous Membrane - immunology, Mucous Membrane - innervation, Mucous Membrane - metabolism, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Neurons - metabolism, Organ Specificity, Receptors, G-Protein-Coupled - agonists, Receptors, G-Protein-Coupled - genetics, Receptors, G-Protein-Coupled - metabolism, Recombinant Fusion Proteins - genetics, Recombinant Fusion Proteins - metabolism, Red Fluorescent Protein, Vertebrates: endocrinology