{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T14:29:16Z","timestamp":1776954556351,"version":"3.51.4"},"reference-count":64,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,12,6]],"date-time":"2011-12-06T00:00:00Z","timestamp":1323129600000},"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":[[2012,1]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>ATP is released in response to cellular damage, and P2X7 receptors have an essential role in the onset and maintenance of pathological changes. Haemorrhagic cystitis (HC) is a well\u2010known adverse effect of therapy with cyclophosphamide used for the treatment of many solid tumours and autoimmune conditions. Here we have evaluated the role of P2X7 receptors in a model of HC induced by cyclophosphamide.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>Effects of pharmacological antagonism or genetic deletion of P2X7 receptor on cyclophosphamide\u2010induced HC in mice was assessed by nociceptive and inflammatory measures. In addition, the presence of immunoreactive P2X7 receptors was assessed by immunohistochemistry.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>Pretreatment with the selective P2X7 receptor antagonist A\u2010438079 or genetic ablation of P2X7 receptors reduced nociceptive behaviour scores in the HC model. The same strategies decreased both oedema and haemorrhage indices, on macroscopic or histological evaluation. Treatment with A\u2010438079 decreased the staining for c\u2010Fos in the lumbar spinal cord and brain cortical areas. Treatment with A\u2010438079 also prevented the increase of urinary bladder myeloperoxidase activity and macrophage migration induced by cyclophosphamide and reduced the tissue levels of IL\u20101\u03b2 and TNF\u2010\u03b1. Finally, P2X7 receptors were markedly up\u2010regulated in the bladders of mice with cyclophosphamide\u2010induced HC.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>P2X7 receptors were significantly involved in a model of HC induced by cyclophosphamide. Pharmacological inhibition of these receptors might represent a new therapeutic option for this pathological condition.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01535.x","type":"journal-article","created":{"date-parts":[[2011,6,15]],"date-time":"2011-06-15T11:12:32Z","timestamp":1308136352000},"page":"183-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["The role of P2X7 purinergic receptors in inflammatory and nociceptive changes accompanying cyclophosphamide\u2010induced haemorrhagic cystitis in mice"],"prefix":"10.1111","volume":"165","author":[{"given":"JP","family":"Martins","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RBM","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Coutinho\u2010Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"CM","family":"Takiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AMO","family":"Battastini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FB","family":"Morrone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MM","family":"Campos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,12,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01649_1.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.10.018"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2006001100011"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00118.2004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000079766.49550.94"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.1.5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-6497-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161209788186335"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2010.09926.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v26.i6.30"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000549"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.01.002"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2006.00404.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2005.10.003"},{"key":"e_1_2_8_16_1","first-page":"565","article-title":"Prophylactic intravesical instillation of epinephrine prevents cyclophosphamide\u2010induced hemorrhagic cystitis in rats","volume":"232","author":"Chow YC","year":"2007","journal-title":"Exp Biol Med (Maywood)"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-009-9138-2"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410X.1996.01146.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.07.002"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707265"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00233.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.042077"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706327"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.3.1451"},{"key":"e_1_2_8_25_1","first-page":"401","article-title":"The incidence of hemorrhagic cystitis and BK\u2010viruria in allogeneic hematopoietic stem cell recipients according to intensity of the conditioning regimen","volume":"91","author":"Giraud G","year":"2006","journal-title":"Haematologica"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5001804"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjq014"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)44929-9"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2010.08.021"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.111559"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.05.018"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00228.2008"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.09.032"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707266"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.12.6436"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006006"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0407"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00229-1"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970-1591.65380"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0400-0"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0241OC"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.03.035"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X1999001000006"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.1999.00310.x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2005.05577.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm051202e"},{"key":"e_1_2_8_47_1","first-page":"112","article-title":"Interstitial cystitis: characterization and management of an enigmatic urologic syndrome","volume":"4","author":"Nickel JC","year":"2002","journal-title":"Rev Urol"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.2001.02179.x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)66403-8"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1053\/eujp.1998.0105"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1839"},{"key":"e_1_2_8_52_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0031-6997(24)01373-5","article-title":"Receptors for purines and pyrimidines","volume":"50","author":"Ralevic V","year":"1998","journal-title":"Pharmacol Rev"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201003-0359OC"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-010-0555-0"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-138883"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00552.2004"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100630"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.06.061"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2004.04858.x"},{"key":"e_1_2_8_60_1","first-page":"591","article-title":"[Hemorrhagic cystitis: etiology and treatment]","volume":"11","author":"Traxer O","year":"2001","journal-title":"Prog Urol"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.278.4.R1027"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.279.1.R295"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.05.043"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1999.5680"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.30.671"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1476-5381.2011.01535.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1476-5381.2011.01535.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T05:56:37Z","timestamp":1741240597000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2011.01535.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,6]]},"references-count":64,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1]]}},"alternative-id":["10.1111\/j.1476-5381.2011.01535.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1476-5381.2011.01535.x","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,6]]},"assertion":[{"value":"2011-12-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}