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

肠内分泌细胞 肽YY 胰多肽 生物 血管活性肠肽 人口 内科学 胃泌素 内分泌学 分子生物学 嗜铬细胞 受体 生物化学 神经肽Y受体 神经肽 胰高血糖素 分泌物 血清素 医学 环境卫生 激素 内分泌系统
作者
Mark K. Nøhr,M. Hauge,Andreas Gille,Kristoffer L. Egerod,Maja S. Engelstoft,Anna Sofie Husted,Rasmus M. Sichlau,Kaare V. Grunddal,Steen Seier Poulsen,Sangdon Han,Robert M. Jones,Stefan Offermanns,Thue W. Schwartz
出处
期刊:Endocrinology [The Endocrine Society]
卷期号:154 (10): 3552-3564 被引量:488
标识
DOI:10.1210/en.2013-1142
摘要

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.
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