{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T11:21:10Z","timestamp":1770290470350,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:00:00Z","timestamp":1752278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201906350225"],"award-info":[{"award-number":["201906350225"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008791","name":"Bayer CropScience","doi-asserted-by":"publisher","award":["200610"],"award-info":[{"award-number":["200610"]}],"id":[{"id":"10.13039\/100008791","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Asthma is characterized by airway hyperresponsiveness (AHR), allergic inflammation, and airway remodelling. Although recent studies have shown that asthma pathophysiology involves P2X4 receptor activation, a potential link with chronic asthma remains to be explored. We investigated the effect of a novel P2X4 receptor antagonist BR11595 on allergen\u2010induced airway responses in a guinea pig model of chronic asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Sensitized guinea pigs were exposed to saline or ovalbumin (OVA) once weekly via aerosolization for 12\u2009weeks. BR11595 (10\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) was injected intraperitoneally five times per week, for four different regimens: all 12\u2009weeks, first 6\u00a0weeks, last 6\u00a0weeks, or last week only. Airway responsiveness to histamine was assessed 24\u2009h before and 6\u00a0h after OVA exposure in weeks 1, 6, and 12. Lung tissue inflammation and remodelling were determined 24\u2009h after the last OVA exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>OVA induced AHR at weeks 1, 6, and 12 compared with saline\u2010challenged animals. The AHR was less pronounced in week 12 compared with week 1. BR11595 significantly reduced OVA\u2010induced AHR in week 6 in guinea pigs treated with BR11595 for 6\u00a0weeks. AHR in week 12 was reduced after BR11595 treatment in week 12 only, next to OVA\u2010induced eosinophilia and Goblet cell hyperplasia, indicating an acute role of P2X4 receptors on chronic inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The P2X4\u2010receptor antagonist BR11595 acutely inhibits AHR, eosinophilia, and Goblet cell hyperplasia after 12\u2009weeks, indicating its potential as a therapeutic target for acute intervention of chronic asthma attacks or exacerbations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70127","type":"journal-article","created":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T07:00:37Z","timestamp":1752303637000},"page":"5378-5390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of the P2RX4 antagonist BR11595 in a guinea pig model of chronic asthma"],"prefix":"10.1111","volume":"182","author":[{"given":"Dan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute of Pharmacy  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoeke A.","family":"Baarsma","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute of Pharmacy  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Mol\u2010van der Veen","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute of Pharmacy  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicky","family":"Verschut","sequence":"additional","affiliation":[{"name":"Aquilo BV  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberley S.","family":"Belfor","sequence":"additional","affiliation":[{"name":"Aquilo BV  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute of Pharmacy  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harm","family":"Maarsingh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Lloyd L. 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