https://m2.mtmt.hu/ eng 2026-10-25 19:03 JournalArticle 2729261 VALIDATED true Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083 Budapest, Hungary János Szentágothai School of Neurosciences, Semmelweis University School of Ph.D Studies, Budapest, Hungary Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, H-1089 Budapest, Hungary Medical Gene Technology Unit, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083 Budapest, Hungary Department of Pharmacology and Toxicology, University of Bonn, D-53105 Bonn, Germany Department of Chemistry, Faculty of Science, Sultan Qaboos University, P. O. Box 36, Postal Code 123, Muscat, Oman PharmaCenter Bonn, Pharmaceutical Institute, University of Bonn, D-53119, Germany Cited By :69 Export Date: 9 June 2023 CODEN: NUDIE Correspondence Address: Sperlágh, B.; Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083 Budapest, Hungary; email: sperlagh@koki.hu Chemicals/CAS: cangrelor, 163706-06-7, 163706-36-3; cibacron blue f3ga, 12236-82-7, 53127-08-5; clopidogrel, 113665-84-2, 120202-66-6, 90055-48-4, 94188-84-8; Freund adjuvant, 9007-81-2; oxidopamine, 1199-18-4, 28094-15-7, 636-00-0; suramin, 129-46-4, 145-63-1; ticlopidine, 53885-35-1, 55142-85-3; cyclic AMP, 60-92-4; Analgesics; Cyclic AMP; Cytokines; P2RY12 protein, human; P2ry12 protein, mouse; P2ry12 protein, rat; Receptors, Purinergic P2Y12 Tradenames: mrs 2395, Sigma Aldrich; psb 0739 Manufacturers: Sanofi Aventis, Hungary; Medicines, United States; Sigma Aldrich; Tocris; Bayer, Germany; Teva, Hungary Funding details: KTIA_13_NAP-A-III/1 Funding details: TÉT_10-1-2011-0050 Funding details: Wellcome Trust, WT Funding details: Seventh Framework Programme, FP7, 294313 Funding details: European Research Council, ERC Funding details: Gedeon Richter, 4700136840 Funding details: Hungarian Scientific Research Fund, OTKA, NN107234, NN79957 Funding text 1: This study was supported by research grants from the Hungarian Research and Development Fund (Grants NN79957 and NN107234 to B.S.), the Hungarian Office of Science and Technology (Grant TÉT_10-1-2011-0050 to B.S.), the European Research Council (Grant 294313-SERRACO to B.S.), the Hungarian Brain Research Program [ KTIA_13_NAP-A-III/1 ] and the Richter Gedeon Plc ( 4700136840 ). The P2ry12 −/− mouse line has been funded by the Wellcome Trust. The authors thank Ádám Dénes for helpful discussions, Ed Beamer for editing the manuscript, and Petra Spitzlei (Department of Pharmacology and Toxicology, University of Bonn, Bonn, Germany) for expert technical assistance. 0 2017-06-08T10:06:06.000+0000 false 2729261 2026-10-16T18:58:27.921+0000 2023-02-01T14:29:37.390+0000 2014-09-09T10:51:26.000+0000 true 10008942 Sperlágh Beáta /api/author/10008942 Author true 10008942 2026-01-12T09:29:14.313+0000 2026-01-12T09:29:14.313+0000 2023-02-01T14:29:37.665+0000 true 10062250 Molnár-Taga Márta /api/admin/10062250 Admin true 10062250 Admin 10066925 /api/admin/10066925 Nemec Évi true true Admin 10067876 /api/admin/10067876 Ladányi Gusztáv true true 2024-10-17T16:20:19.023+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Horvath, G Central P2Y12 receptor blockade alleviates inflammatory and neuropathic pain and cytokine production in rodents. true true /api/journal/14239 REVIEWED true false 14239 false 14239 true 0969-9961 1095-953X Journal FOREIGN 70 162 178 162 17 2014 In this study the role of P2Y12 receptors (P2Y12R) was explored in rodent models of inflammatory and neuropathic pain and in acute thermal nociception. In correlation with their activity to block the recombinant human P2Y12R, the majority of P2Y12R antagonists alleviated mechanical hyperalgesia dose-dependently, following intraplantar CFA injection, and after partial ligation of the sciatic nerve in rats. They also caused an increase in thermal nociceptive threshold in the hot plate test. Among the six P2Y12R antagonists evaluated in the pain studies, the selective P2Y12 receptor antagonist PSB-0739 was most potent upon intrathecal application. P2Y12R mRNA and IL-1beta protein were time-dependently overexpressed in the rat hind paw and lumbar spinal cord following intraplantar CFA injection. This was accompanied by the upregulation of TNF-alpha, IL-6 and IL-10 in the hind paw. PSB-0739 (0.3mg/kg i.t.) attenuated CFA-induced expression of cytokines in the hind paw and of IL-1beta in the spinal cord. Subdiaphragmatic vagotomy and the alpha7 nicotinic acetylcholine receptor antagonist MLA occluded the effect of PSB-0739 (i.t.) on pain behavior and peripheral cytokine induction. Denervation of sympathetic nerves by 6-OHDA pretreatment did not affect the action of PSB-0739. PSB-0739, in an analgesic dose, did not influence motor coordination and platelet aggregation. Genetic deletion of the P2Y12R in mice reproduced the effect of P2Y12R antagonists on mechanical hyperalgesia in inflammatory and neuropathic pain models, on acute thermal nociception and on the induction of spinal IL-1beta. Here we report the robust involvement of the P2Y12R in inflammatory pain. The anti-hyperalgesic effect of P2Y12R antagonism could be mediated by the inhibition of both central and peripheral cytokine production and involves alpha7-receptor mediated efferent pathways. 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/api/keyword/2561346 true true SjrRating 11097254 /api/sjrrating/11097254 9 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr true true ClassificationExternal 2808 /api/classificationexternal/2808 true 2808 true D1 DIRECT true true /api/publication/2729261 <div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10048592"><a href="/gui2/?type=authors&mode=browse&sel=10048592" target="_blank">Horvath G (<span class="authorship-author-name">Horváth Gergely</span> <span class="authorAux-mtmt"> biológia</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular 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D. Studies</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10052098"><a href="/gui2/?type=authors&mode=browse&sel=10052098" target="_blank">Goloncser F (<span class="authorship-author-name">Gölöncsér Flóra</span> <span class="authorAux-mtmt"> idegtudományok</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology; <span title="Semmelweis University">SU</span>/School of Ph. D. Studies</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="228"><a href="/gui2/?type=authors&mode=browse&sel=228" target="_blank">Csolle C (<span class="authorship-author-name">Csölle Cecília</span> <span class="authorAux-mtmt"> Farmakológia</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology; <span title="Semmelweis University">SU</span>/School of Ph. D. Studies</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10015480"><a href="/gui2/?type=authors&mode=browse&sel=10015480" target="_blank">Kiraly K (<span class="authorship-author-name">Király Kornél P</span> <span class="authorAux-mtmt"> Farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="207"><a href="/gui2/?type=authors&mode=browse&sel=207" target="_blank">Ando RD (<span class="authorship-author-name">Andó Rómeó</span> <span class="authorAux-mtmt"> Molekuláris farmakológia</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="91"><a href="/gui2/?type=authors&mode=browse&sel=91" target="_blank">Baranyi M (<span class="authorship-author-name">Baranyi Mária</span> <span class="authorAux-mtmt"> Molekuláris farmakológia</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10057984"><a href="/gui2/?type=authors&mode=browse&sel=10057984" target="_blank">Kovanyi B (<span class="authorship-author-name">Koványi Bence</span> <span class="authorAux-mtmt"> Idegtudományok</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology; <span title="Semmelweis University">SU</span>/School of Ph. D. Studies</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="198"><a href="/gui2/?type=authors&mode=browse&sel=198" target="_blank">Mate Z (<span class="authorship-author-name">Máté Zoltán</span> <span class="authorAux-mtmt"> Molekuláris biológia, genetika</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Gene Technology and Developmental Neurobiology">DGTDN</span>/Laboratory of Molecular Biology and Genetics</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Hoffmann K </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Algaier I </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Baqi Y </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Muller CE </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Von Kugelgen I </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10008942"><a href="/gui2/?type=authors&mode=browse&sel=10008942" target="_blank">Sperlagh B ✉ (<span class="authorship-author-name">Sperlágh Beáta</span> <span class="authorAux-mtmt"> Neurofarmakológia</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;2729261" target="_blank">Central P2Y12 receptor blockade alleviates inflammatory and neuropathic pain and cytokine production in rodents.</a></div> <div> <span class="journal-title">NEUROBIOLOGY OF DISEASE</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0969-9961">0969-9961</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1095-953X">1095-953X</a>)</span>: <span class="journal-volume">70</span> <span class="page"> pp 162-178 </span> <span class="year">(2014)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1016/j.nbd.2014.06.011" target="_blank" href="https://doi.org/10.1016/j.nbd.2014.06.011"> DOI </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:black" title="30856" target="_blank" href="https://real.mtak.hu/30856"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000340691400016" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000340691400016"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="84904576142" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-84904576142"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="24971933" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=24971933&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Neurology&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 88</span> | Independent citation: 78 | Self citation: 10 | Unknown citation: 0 | Number of citations in WoS: 80 | Number of citations in Scopus:&nbsp;86 | WoS/Scopus assigned:&nbsp;88 | Number of citations with DOI:&nbsp;88 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;2729261&sort=publishedYear,desc&sort=title"> Number of cited publications: 7 </a> </div> <div class="mtid"><span class="long-pub-mtid">Publication: 2729261</span> | <span class="status-data status-VALIDATED"> Validated </span> <span class="oldId">Old id: 2729261</span> | Core Citing | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">MEDLINE</span> </div> <div class="funder"> Hungarian Scientific Research Fund(NN79957), Hungarian Scientific Research Fund(NN107234), European Research Council(294313-SERRACO), TÉT(10-1-2011-0050), (KTIA_13_NAP-A-III/1) </div> <div class="lastModified">Last Modified: 2023.02.01. 15:29 Márta Molnár-Taga (SE 4-es admin) </div> <div class="lockedBy">Centrally managed 2024.10.17. 18:20 Évi Nemec (MTMT Központi 3, admin) Gusztáv Ladányi (MTMT API user, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Comments</u>: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083 Budapest, Hungary János Szentágothai School of Neurosciences, Semmelweis University School of Ph.D Studies, Budapest, Hungary Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, H-10...</pre> </div></div>