Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine
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Authors
Koo, Ada
Pustovit, Ruslan V
Woodward, Orla RM
Lewis, Jo E
Gribble, Fiona M
Hossain, Mohammed Akhter
Furness, John B
Journal Title
Cell and Tissue Research
ISSN
0302-766X
Publisher
Springer
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Reimann, F., Koo, A., Pustovit, R. V., Woodward, O. R., Lewis, J. E., Gribble, F. M., Hossain, M. A., & et al. Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine. Cell and Tissue Research https://doi.org/10.17863/CAM.84415
Abstract
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.
Sponsorship
Wellcome Trust (100574/Z/12/Z)
Wellcome Trust (106262/Z/14/Z)
MRC (MC_UU_00014/3)
Embargo Lift Date
2025-05-10
Identifiers
This record's DOI: https://doi.org/10.17863/CAM.84415
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336995
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