α-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats

Abstract The central nervous system is involved in regulation of defaecation. It is generally considered that supraspinal regions control the spinal defaecation centre. However, signal transmission from supraspinal regions to the spinal defaecation centre is still unclear. In this study, we investig...

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Autores principales:	Hiromi H. Ueda, Kiyotada Naitou, Hiroyuki Nakamori, Kazuhiro Horii, Takahiko Shiina, Tatsunori Masatani, Mitsuya Shiraishi, Yasutake Shimizu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3364da7d49cc4cee83da194773133382
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spelling	oai:doaj.org-article:3364da7d49cc4cee83da1947731333822021-12-02T15:22:57Zα-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats10.1038/s41598-020-80020-x2045-2322https://doaj.org/article/3364da7d49cc4cee83da1947731333822021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80020-xhttps://doaj.org/toc/2045-2322Abstract The central nervous system is involved in regulation of defaecation. It is generally considered that supraspinal regions control the spinal defaecation centre. However, signal transmission from supraspinal regions to the spinal defaecation centre is still unclear. In this study, we investigated the regulatory role of an anorexigenic neuropeptide, α-MSH, in the spinal defaecation centre in rats. Intrathecal administration of α-MSH to the L6-S1 spinal cord enhanced colorectal motility. The prokinetic effect of α-MSH was abolished by severing the pelvic nerves. In contrast, severing the colonic nerves or thoracic cord transection at the T4 level had no impact on the effect of α-MSH. RT-PCR analysis revealed MC1R mRNA and MC4R mRNA expression in the L6-S1 spinal cord. Intrathecally administered MC1R agonists, BMS470539 and SHU9119, mimicked the α-MSH effect, but a MC4R agonist, THIQ, had no effect. These results demonstrate that α-MSH binds to MC1R in the spinal defaecation centre and activates pelvic nerves, leading to enhancement of colorectal motility. This is, to our knowledge, the first report showing the functional role of α-MSH in the spinal cord. In conclusion, our findings suggest that α-MSH is a candidate for a neurotransmitter from supraspinal regions to the spinal defaecation centre.Hiromi H. UedaKiyotada NaitouHiroyuki NakamoriKazuhiro HoriiTakahiko ShiinaTatsunori MasataniMitsuya ShiraishiYasutake ShimizuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiromi H. Ueda Kiyotada Naitou Hiroyuki Nakamori Kazuhiro Horii Takahiko Shiina Tatsunori Masatani Mitsuya Shiraishi Yasutake Shimizu α-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats
description	Abstract The central nervous system is involved in regulation of defaecation. It is generally considered that supraspinal regions control the spinal defaecation centre. However, signal transmission from supraspinal regions to the spinal defaecation centre is still unclear. In this study, we investigated the regulatory role of an anorexigenic neuropeptide, α-MSH, in the spinal defaecation centre in rats. Intrathecal administration of α-MSH to the L6-S1 spinal cord enhanced colorectal motility. The prokinetic effect of α-MSH was abolished by severing the pelvic nerves. In contrast, severing the colonic nerves or thoracic cord transection at the T4 level had no impact on the effect of α-MSH. RT-PCR analysis revealed MC1R mRNA and MC4R mRNA expression in the L6-S1 spinal cord. Intrathecally administered MC1R agonists, BMS470539 and SHU9119, mimicked the α-MSH effect, but a MC4R agonist, THIQ, had no effect. These results demonstrate that α-MSH binds to MC1R in the spinal defaecation centre and activates pelvic nerves, leading to enhancement of colorectal motility. This is, to our knowledge, the first report showing the functional role of α-MSH in the spinal cord. In conclusion, our findings suggest that α-MSH is a candidate for a neurotransmitter from supraspinal regions to the spinal defaecation centre.
format	article
author	Hiromi H. Ueda Kiyotada Naitou Hiroyuki Nakamori Kazuhiro Horii Takahiko Shiina Tatsunori Masatani Mitsuya Shiraishi Yasutake Shimizu
author_facet	Hiromi H. Ueda Kiyotada Naitou Hiroyuki Nakamori Kazuhiro Horii Takahiko Shiina Tatsunori Masatani Mitsuya Shiraishi Yasutake Shimizu
author_sort	Hiromi H. Ueda
title	α-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats
title_short	α-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats
title_full	α-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats
title_fullStr	α-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats
title_full_unstemmed	α-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats
title_sort	α-msh-induced activation of spinal mc1r but not mc4r enhances colorectal motility in anaesthetised rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3364da7d49cc4cee83da194773133382
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α-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats

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