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Autoradiography of H-3-pirenzepine and H-3-AFDX-384 in Mouse Brain Regions: Possible Insights into M-1, M-2, and M-4 Muscarinic Receptors Distribution
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SYSNO ASEP 0489164 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Autoradiography of H-3-pirenzepine and H-3-AFDX-384 in Mouse Brain Regions: Possible Insights into M-1, M-2, and M-4 Muscarinic Receptors Distribution Author(s) Valuskova, P. (CZ)
Farar, V. (CZ)
Forczek, Sándor (UEB-Q) RID, ORCID
Křížová, I. (CZ)
Mysliveček, J. (CZ)Number of authors 5 Article number 124 Source Title Frontiers in Pharmacology. - : Frontiers Media - ISSN 1663-9812
Roč. 9, FEB 20 (2018)Number of pages 15 s. Language eng - English Country CH - Switzerland Keywords 3 h-afdx-384 ; 3 H-pirenzepine ; 3 h-qnb ; Autoradiography ; M muscarinic receptor 1 ; M muscarinic receptor 2 ; M muscarinic receptor 4 Subject RIV FH - Neurology OECD category Neurosciences (including psychophysiology Institutional support UEB-Q - RVO:61389030 UT WOS 000425516600001 EID SCOPUS 85042220474 DOI 10.3389/fphar.2018.00124 Annotation Autoradiography helps to determine the distribution and density of muscarinic receptor (MR) binding sites in the brain. However, it relies on the selectivity of radioligands toward their target. 3 H-Pirenzepine is commonly believed to label predominantly M 1 MR, 3 H-AFDX-384 is considered as M 2 MR selective ligand. Here we performed series of autoradiographies with 3 H-AFDX-384 (2 nM), and 3 H-pirenzepine (5 nM) in WT, M 1 KO, M 2 KO, and M 4 KO mice to address the ligand selectivity. Labeling with 3 H-pirenzepine using M 1 KO, M 2 KO, and M 4 KO brain sections showed the high selectivity toward M 1 MR. Selectivity of 3 H-AFDX-384 toward M 2 MR varies among brain regions and depends on individual MR subtype proportion. All binding sites in the medulla oblongata and pons, correspond to M 2 MR. In caudate putamen, nucleus accumbens and olfactory tubercle, 77.7, 74.2, and 74.6% of 3 H-AFDX-384 binding sites, respectively, are represented by M 4 MR and M 2 MR constitute only a minor portion. In cortex and hippocampus, 3 H-AFDX-384 labels almost similar amounts of M 2 MR and M 4 MR alongside significant amounts of non-M 2 /non-M 4 MR. In cortex, the proportion of 3 H-AFDX-384 binding sites attributable to M 2 MR can be increased by blocking M 4 MR with MT3 toxin without affecting non-M 4 MR. PD102807, which is considered as a highly selective M 4 MR antagonist failed to improve the discrimination of M 2 MR. Autoradiography with 3 H-QNB showed genotype specific loss of binding sites. In conclusion: while 3 H-pirenzepine showed the high selectivity toward M 1 MR, 3 H-AFDX-384 binding sites represent different populations of MR subtypes in a brain-region-specific manner. This finding has to be taken into account when interpreting the binding data. Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2019
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