2. Academic Validation
  3. All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium

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

  • Sci Rep. 2017 Jul 11;7(1):5083. doi: 10.1038/s41598-017-05384-z.
Beatrice Mihaela Radu 1 2,  Antonio Marco Maria Osculati 3,  Eda Suku 4,  Adela Banciu 2 5,  Grygoriy Tsenov 1,  Flavia Merigo 1,  Marzia Di Chio 6,  Daniel Dumitru Banciu 2,  Cristina Tognoli 1,  Petr Kacer 7,  Alejandro Giorgetti 4,  Mihai Radu 8 9,  Giuseppe Bertini 1,  Paolo Francesco Fabene 1
Affiliations

Affiliations

  • 1 Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, 37134, Italy.
  • 2 Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, 050095, Romania.
  • 3 Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, 27100, Italy.
  • 4 Department of Biotechnology, University of Verona, Verona, 37134, Italy.
  • 5 Engineering Faculty, Constantin Brancusi' University, Calea Eroilor 30, Targu Jiu, 210135, Romania.
  • 6 Department of Public Health and Community Medicine, University of Verona, Verona, 37134, Italy.
  • 7 National Institute of Mental Health, Klecany, 25067, Czech Republic.
  • 8 Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, 37134, Italy. mihai.radu@univr.it.
  • 9 Department of Life and Environmental Physics, Horia Hulubei National Institute for Physics and Nuclear Engineering, PO Box MG-6, Reactorului 30, Magurele, 077125, Romania. mihai.radu@univr.it.
PMID: 28698560 DOI: 10.1038/s41598-017-05384-z
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.

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