{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:23:28Z","timestamp":1790504608019,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,1,12]],"date-time":"2011-01-12T00:00:00Z","timestamp":1294790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:sec><jats:title>BACKGROUND AND PURPOSE<\/jats:title><jats:p>In osteoarthritis (OA), bradykinin (BK) is known to contribute to pain and synovitis, but not to cartilage degradation. Here, we investigated effects of BK and its antagonists on chondrocytes, cells involved in cartilage homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>EXPERIMENTAL APPROACH<\/jats:title><jats:p>BK receptor density and affinities of BK, its analogues and antagonists were measured in cultured human and rat chondrocytes by radioligand binding. Effects of BK were assessed by accumulation of inositol phosphates (IP) and release of interleukin (IL)\u20106 and IL\u20108.<\/jats:p><\/jats:sec><jats:sec><jats:title>KEY RESULTS<\/jats:title><jats:p>Density of [<jats:sup>3<\/jats:sup>H]\u2010BK binding sites was higher (13\u201330\u2010fold) and BK evoked a greater (48\u2010fold) IP production, in human than in rat chondrocytes. The BK B<jats:sub>2<\/jats:sub> receptor antagonists MEN16132 and icatibant displayed similar binding affinity. MEN16132 was 40\u2010fold more potent than icatibant in the IP assay. In human chondrocytes, BK increased release (over 24\u2003h) of IL\u20106 and IL\u20108, effects blocked by MEN16132 but not by the B<jats:sub>1<\/jats:sub> receptor antagonist Lys\u2010[Leu<jats:sup>8<\/jats:sup>][desArg<jats:sup>9<\/jats:sup>]BK. BK\u2010induced release of IL\u20106, but not of IL\u20108, was partially inhibited by indomethacin (10\u2003\u00b5M) and nordihydroguaiaretic acid (10\u2003\u00b5M). Antagonists for the prostanoid EP receptors (AH6809 10\u2003\u00b5M; L\u2010798\u2003196, 200\u2003nM; L\u2010161\u2003982, 1\u2003\u00b5M) were ineffective. Dexamethasone (100\u2003nM) partially inhibited release of both IL\u20106 and IL\u20108. Inhibitors of intracellular downstream signalling pathways (SB203580 10\u2003\u00b5M; PD98059, 30\u2003\u00b5M; SP600125, 30\u2003\u00b5M; BAY\u2010117085, 5\u2003\u00b5M) indicated the involvement of p38 MAPK and the activation of NF\u2010\u03baB.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION AND IMPLICATIONS<\/jats:title><jats:p>BK mediated inflammatory changes and cartilage degradation and B<jats:sub>2<\/jats:sub> receptor blockade would, therefore, be a potential treatment for OA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2010.01062.x","type":"journal-article","created":{"date-parts":[[2010,10,13]],"date-time":"2010-10-13T11:18:02Z","timestamp":1286968682000},"page":"611-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Bradykinin and B<sub>2<\/sub> receptor antagonism in rat and human articular chondrocytes"],"prefix":"10.1111","volume":"162","author":[{"given":"S","family":"Meini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Cucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Catalani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Bellucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Giuliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CA","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,1,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00499.x"},{"key":"e_1_2_8_3_1","first-page":"S236","article-title":"Practical considerations for the pharmacologic management of osteoarthritis","volume":"15","author":"Altman RD","year":"2009","journal-title":"Am J Manag Care"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-007-0328-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01972842"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.03.031"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00511.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(03)00086-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2580861"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2007.01453.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-3109(97)00023-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27290"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22282"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.159657"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705648"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00045391-199602000-00002"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.10.014"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1955.sp001097"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000144484.69656.e4"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.098764"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000144854.66565.8f"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.4049\/jimmunol.144.2.499","article-title":"IL\u20106 production by human articular chondrocytes. 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