All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium

Abstract Clinical and experimental studies indicate that muscarinic acetylcholine receptors are potential pharmacological targets for the treatment of neurological diseases. Although these receptors have been described in human, bovine and rat cerebral microvascular tissue, a subtype functional char...

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Autores principales:	Beatrice Mihaela Radu, Antonio Marco Maria Osculati, Eda Suku, Adela Banciu, Grygoriy Tsenov, Flavia Merigo, Marzia Di Chio, Daniel Dumitru Banciu, Cristina Tognoli, Petr Kacer, Alejandro Giorgetti, Mihai Radu, Giuseppe Bertini, Paolo Francesco Fabene
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/02226d4ad5a34ae38427c894c235be2a
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spelling	oai:doaj.org-article:02226d4ad5a34ae38427c894c235be2a2021-12-02T15:05:46ZAll muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium10.1038/s41598-017-05384-z2045-2322https://doaj.org/article/02226d4ad5a34ae38427c894c235be2a2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05384-zhttps://doaj.org/toc/2045-2322Abstract Clinical and experimental studies indicate that muscarinic acetylcholine receptors are potential pharmacological targets for the treatment of neurological diseases. Although these receptors have been described in human, bovine and rat cerebral microvascular tissue, a subtype functional characterization in mouse brain endothelium is lacking. Here, we show that all muscarinic acetylcholine receptors (M1-M5) are expressed in mouse brain microvascular endothelial cells. The mRNA expression of M2, M3, and M5 correlates with their respective protein abundance, but a mismatch exists for M1 and M4 mRNA versus protein levels. Acetylcholine activates calcium transients in brain endothelium via muscarinic, but not nicotinic, receptors. Moreover, although M1 and M3 are the most abundant receptors, only a small fraction of M1 is present in the plasma membrane and functions in ACh-induced Ca2+ signaling. Bioinformatic analyses performed on eukaryotic muscarinic receptors demonstrate a high degree of conservation of the orthosteric binding site and a great variability of the allosteric site. In line with previous studies, this result indicates muscarinic acetylcholine receptors as potential pharmacological targets in future translational studies. We argue that research on drug development should especially focus on the allosteric binding sites of the M1 and M3 receptors.Beatrice Mihaela RaduAntonio Marco Maria OsculatiEda SukuAdela BanciuGrygoriy TsenovFlavia MerigoMarzia Di ChioDaniel Dumitru BanciuCristina TognoliPetr KacerAlejandro GiorgettiMihai RaduGiuseppe BertiniPaolo Francesco FabeneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Beatrice Mihaela Radu Antonio Marco Maria Osculati Eda Suku Adela Banciu Grygoriy Tsenov Flavia Merigo Marzia Di Chio Daniel Dumitru Banciu Cristina Tognoli Petr Kacer Alejandro Giorgetti Mihai Radu Giuseppe Bertini Paolo Francesco Fabene All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium
description	Abstract Clinical and experimental studies indicate that muscarinic acetylcholine receptors are potential pharmacological targets for the treatment of neurological diseases. Although these receptors have been described in human, bovine and rat cerebral microvascular tissue, a subtype functional characterization in mouse brain endothelium is lacking. Here, we show that all muscarinic acetylcholine receptors (M1-M5) are expressed in mouse brain microvascular endothelial cells. The mRNA expression of M2, M3, and M5 correlates with their respective protein abundance, but a mismatch exists for M1 and M4 mRNA versus protein levels. Acetylcholine activates calcium transients in brain endothelium via muscarinic, but not nicotinic, receptors. Moreover, although M1 and M3 are the most abundant receptors, only a small fraction of M1 is present in the plasma membrane and functions in ACh-induced Ca2+ signaling. Bioinformatic analyses performed on eukaryotic muscarinic receptors demonstrate a high degree of conservation of the orthosteric binding site and a great variability of the allosteric site. In line with previous studies, this result indicates muscarinic acetylcholine receptors as potential pharmacological targets in future translational studies. We argue that research on drug development should especially focus on the allosteric binding sites of the M1 and M3 receptors.
format	article
author	Beatrice Mihaela Radu Antonio Marco Maria Osculati Eda Suku Adela Banciu Grygoriy Tsenov Flavia Merigo Marzia Di Chio Daniel Dumitru Banciu Cristina Tognoli Petr Kacer Alejandro Giorgetti Mihai Radu Giuseppe Bertini Paolo Francesco Fabene
author_facet	Beatrice Mihaela Radu Antonio Marco Maria Osculati Eda Suku Adela Banciu Grygoriy Tsenov Flavia Merigo Marzia Di Chio Daniel Dumitru Banciu Cristina Tognoli Petr Kacer Alejandro Giorgetti Mihai Radu Giuseppe Bertini Paolo Francesco Fabene
author_sort	Beatrice Mihaela Radu
title	All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium
title_short	All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium
title_full	All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium
title_fullStr	All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium
title_full_unstemmed	All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium
title_sort	all muscarinic acetylcholine receptors (m1-m5) are expressed in murine brain microvascular endothelium
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/02226d4ad5a34ae38427c894c235be2a
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All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium

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