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Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine

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 investiga...

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Autores principales: Koo, Ada, Pustovit, Ruslan V., Woodward, Orla R. M., Lewis, Jo E., Gribble, Fiona M., Hossain, Mohammed Akhter, Reimann, Frank, Furness, John B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200676/
https://www.ncbi.nlm.nih.gov/pubmed/35596811
http://dx.doi.org/10.1007/s00441-022-03635-8
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author Koo, Ada
Pustovit, Ruslan V.
Woodward, Orla R. M.
Lewis, Jo E.
Gribble, Fiona M.
Hossain, Mohammed Akhter
Reimann, Frank
Furness, John B.
author_facet Koo, Ada
Pustovit, Ruslan V.
Woodward, Orla R. M.
Lewis, Jo E.
Gribble, Fiona M.
Hossain, Mohammed Akhter
Reimann, Frank
Furness, John B.
author_sort Koo, Ada
collection PubMed
description 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-HT(3) 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-HT(3) receptors of enteric sensory neurons to elicit propulsive reflexes.
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spelling pubmed-92006762022-06-17 Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine Koo, Ada Pustovit, Ruslan V. Woodward, Orla R. M. Lewis, Jo E. Gribble, Fiona M. Hossain, Mohammed Akhter Reimann, Frank Furness, John B. Cell Tissue Res Regular Article 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-HT(3) 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-HT(3) receptors of enteric sensory neurons to elicit propulsive reflexes. Springer Berlin Heidelberg 2022-05-21 2022 /pmc/articles/PMC9200676/ /pubmed/35596811 http://dx.doi.org/10.1007/s00441-022-03635-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Regular Article
Koo, Ada
Pustovit, Ruslan V.
Woodward, Orla R. M.
Lewis, Jo E.
Gribble, Fiona M.
Hossain, Mohammed Akhter
Reimann, Frank
Furness, John B.
Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine
title Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine
title_full Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine
title_fullStr Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine
title_full_unstemmed Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine
title_short Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine
title_sort expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200676/
https://www.ncbi.nlm.nih.gov/pubmed/35596811
http://dx.doi.org/10.1007/s00441-022-03635-8
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