{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:51:47Z","timestamp":1791255107057,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1703,"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":[[2004,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Complement activation is implicated in the pathogenesis of intestinal ischaemia\u2013reperfusion injury (I\/R), although the relative importance of individual complement components is unclear. A C3a receptor antagonist <jats:italic>N<\/jats:italic>(2)\u2010[(2,2\u2010diphenylethoxy)acetyl]\u2010<jats:sc>L<\/jats:sc>\u2010arginine (C3aRA) has been compared with a C5a receptor antagonist (C5aRA), AcF\u2010[OPdChaWR], in a rat model of intestinal I\/R.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>C3aRA (IC<jats:sub>50<\/jats:sub>=0.15 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) and C5aRA (IC<jats:sub>50<\/jats:sub>=0.32 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) bound selectively to human polymorphonuclear leukocyte (PMN) C3a and C5a receptors, respectively. Effects on circulating neutrophils and blood pressure in the rat were also assessed.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Anaesthetised rats, subjected to intestinal ischaemia (30 min) and reperfusion (120 min), were administered intravenously with either (A) the C3aRA (0.1\u20131.0 mg kg<jats:sup>\u22121<\/jats:sup>); the C5aRA (1.0 mg kg<jats:sup>\u22121<\/jats:sup>); the C3aRA+C5aRA (each 1.0 mg kg<jats:sup>\u22121<\/jats:sup>); or vehicle, 45 min prior, or (B) the C3aRA (1.0 mg kg<jats:sup>\u22121<\/jats:sup>) or vehicle, 120 min prior to reperfusion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The C3aRA and C5aRA, administered 45 min prior to reperfusion, displayed similar efficacies at ameliorating several disease markers (increased oedema, elevated ALT levels and mucosal damage) of rat intestinal I\/R. The combination drug treatment did not result in greater injury reduction than either antagonist alone. However, doses of the C3aRA (0.01\u201310 mg kg<jats:sup>\u22121<\/jats:sup>) caused transient neutropaenia, and the highest dose (10 mg kg<jats:sup>\u22121<\/jats:sup>) also caused a rapid and transient hypertension.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The C3aRA (1.0 mg kg<jats:sup>\u22121<\/jats:sup>), delivered 120 min prior to reperfusion to remove the global effect of C3aRA\u2010induced neutrophil sequestration, did not attenuate the markers of intestinal I\/R, despite persistent C3aR antagonism at this time.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>C3aR antagonism does not appear to be responsible for the anti\u2010inflammatory actions of this C3aRA in intestinal I\/R in the rat. Instead, C3aRA\u2010mediated global neutrophil tissue sequestration during ischaemia and early reperfusion may account for the protective effects observed.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>142<\/jats:bold>, 756\u2013764. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705819\">10.1038\/sj.bjp.0705819<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705819","type":"journal-article","created":{"date-parts":[[2004,6,17]],"date-time":"2004-06-17T17:18:11Z","timestamp":1087492691000},"page":"756-764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Comparative anti\u2010inflammatory activities of antagonists to C3a and C5a receptors in a rat model of intestinal ischaemia\/reperfusion injury"],"prefix":"10.1111","volume":"142","author":[{"given":"Lavinia M","family":"Proctor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiruma V","family":"Arumugam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Shiels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P","family":"Fairlie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/rtph.1998.1201"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.10.6341"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000051920"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00737.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.2002.6369"},{"key":"e_1_2_7_7_1","first-page":"1600","article-title":"Is the gut responsible for multiple organ failure?","volume":"129","author":"BION J.F.","year":"1999","journal-title":"Schweiz Med. 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