Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine
| Autor: | Koo, Ada, Pustovit, Ruslan V, Woodward, Orla RM, Lewis, Jo E, Gribble, Fiona M, Hossain, Mohammed Akhter, Reimann, Frank, Furness, John B |
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| Přispěvatelé: | Koo, Ada [0000-0003-2414-0852], Pustovit, Ruslan V [0000-0002-9221-1811], Furness, John B [0000-0002-0219-3438], Apollo - University of Cambridge Repository, Reimann, Frank [0000-0001-9399-6377] |
| Rok vydání: | 2022 |
| Předmět: | |
| Popis: | Funder: University of Melbourne The gastrointestinal hormone, insulin-like peptide 5 (INSL5), is found in large intestinal enteroendocrine cells (EEC). One of its functions is to stimulate nerve circuits that increase propulsive activity of the colon through its receptor, the relaxin family peptide 4 receptor (RXFP4). To investigate the mechanisms that link INSL5 to stimulation of propulsion, we have determined the localisation of cells expressing Rxfp4 in the mouse colon, using a reporter mouse to locate cells expressing the gene. The fluorescent signal indicating the location of Rxfp4 expression was in EEC, the greatest overlap of Rxfp4-dependent labelling being with cells containing 5-HT. In fact, > 90% of 5-HT cells were positive for Rxfp4 labelling. A small proportion of cells with Rxfp4-dependent labelling was 5-HT-negative, 11-15% in the distal colon and rectum, and 35% in the proximal colon. Of these, some were identified as L-cells by immunoreactivity for oxyntomodulin. Rxfp4-dependent fluorescence was also found in a sparse population of nerve endings, where it was colocalised with CGRP. We used the RXFP4 agonist, INSL5-A13, to activate the receptor and probe the role of the 5-HT cells in which it is expressed. INSL5-A13 administered by i.p. injection to conscious mice caused an increase in colorectal propulsion that was antagonised by the 5-HT3 receptor blocker, alosetron, also given i.p. We conclude that stimuli that excite INSL5-containing colonic L-cells release INSL5 that, through RXFP4, excites 5-HT release from neighbouring endocrine cells, which in turn acts on 5-HT3 receptors of enteric sensory neurons to elicit propulsive reflexes. |
| Databáze: | OpenAIRE |
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