COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat

Departments of 1  Neurology, 2  Anatomy and Neurobiology, and 3  Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405 The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute...

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Veröffentlicht in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2003-02, Vol.284 (2), p.574-R585
Hauptverfasser: Hu, V. Y, Malley, S, Dattilio, A, Folsom, J. B, Zvara, P, Vizzard, M. A
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container_end_page R585
container_issue 2
container_start_page 574
container_title American journal of physiology. Regulatory, integrative and comparative physiology
container_volume 284
creator Hu, V. Y
Malley, S
Dattilio, A
Folsom, J. B
Zvara, P
Vizzard, M. A
description Departments of 1  Neurology, 2  Anatomy and Neurobiology, and 3  Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405 The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute (4 h), intermediate (48 h), or chronic (10 day) cyclophosphamide (CYP)-induced cystitis. Bladders were harvested from euthanized female rats for analyses. Conscious cystometry was used to assess the effects of a COX-2-specific inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl2(5 H )-furanone (DFU, 5 mg/kg sc), a disubstituted furanone, in CYP-induced cystitis. COX-2 mRNA was increased in inflamed bladders after acute (12-fold) and chronic (9-fold) treatment. COX-2 protein expression in inflamed bladders paralleled COX-2 mRNA expression. Prostaglandin D 2 -methoxime expression in the bladder was significantly ( P    0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E 2 was significantly ( P    0.01) increased (2-fold) in the bladder with intermediate (1.7-fold) and chronic (2.6-fold) cystitis. COX-2-immunoreactive cell profiles were distributed throughout the inflamed bladder and coexpressed histamine immunoreactivity. Conscious cystometry in rats treated with CYP + DFU showed increased micturition intervals 4 and 48 h after CYP treatment and decreased intravesical pressures during filling and micturition compared with rats treated with CYP + vehicle. These studies suggest an involvement of urinary bladder COX-2 and its metabolites in altered micturition reflexes with CYP-induced cystitis. inflammation; prostaglandins; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5 H )-furanone; mast cells; cystometry
doi_str_mv 10.1152/ajpregu.00465.2002
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Y ; Malley, S ; Dattilio, A ; Folsom, J. B ; Zvara, P ; Vizzard, M. A</creator><creatorcontrib>Hu, V. Y ; Malley, S ; Dattilio, A ; Folsom, J. B ; Zvara, P ; Vizzard, M. A</creatorcontrib><description>Departments of 1  Neurology, 2  Anatomy and Neurobiology, and 3  Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405 The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute (4 h), intermediate (48 h), or chronic (10 day) cyclophosphamide (CYP)-induced cystitis. Bladders were harvested from euthanized female rats for analyses. Conscious cystometry was used to assess the effects of a COX-2-specific inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl2(5 H )-furanone (DFU, 5 mg/kg sc), a disubstituted furanone, in CYP-induced cystitis. COX-2 mRNA was increased in inflamed bladders after acute (12-fold) and chronic (9-fold) treatment. COX-2 protein expression in inflamed bladders paralleled COX-2 mRNA expression. Prostaglandin D 2 -methoxime expression in the bladder was significantly ( P    0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E 2 was significantly ( P    0.01) increased (2-fold) in the bladder with intermediate (1.7-fold) and chronic (2.6-fold) cystitis. COX-2-immunoreactive cell profiles were distributed throughout the inflamed bladder and coexpressed histamine immunoreactivity. Conscious cystometry in rats treated with CYP + DFU showed increased micturition intervals 4 and 48 h after CYP treatment and decreased intravesical pressures during filling and micturition compared with rats treated with CYP + vehicle. These studies suggest an involvement of urinary bladder COX-2 and its metabolites in altered micturition reflexes with CYP-induced cystitis. inflammation; prostaglandins; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5 H )-furanone; mast cells; cystometry</description><identifier>ISSN: 0363-6119</identifier><identifier>EISSN: 1522-1490</identifier><identifier>DOI: 10.1152/ajpregu.00465.2002</identifier><identifier>PMID: 12388444</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Blotting, Western ; Cyclooxygenase 2 ; Cyclophosphamide - administration &amp; dosage ; Cyclophosphamide - pharmacology ; Cystitis - chemically induced ; Cystitis - enzymology ; Cystitis - metabolism ; Cystitis - physiopathology ; Dinoprostone - metabolism ; Drug Administration Schedule ; Female ; Furans - pharmacology ; Gene Expression Regulation - drug effects ; Immunoenzyme Techniques ; Immunohistochemistry ; Isoenzymes - antagonists &amp; inhibitors ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Prostaglandin D2 - analogs &amp; derivatives ; Prostaglandin D2 - metabolism ; Prostaglandin-Endoperoxide Synthases - genetics ; Prostaglandin-Endoperoxide Synthases - metabolism ; Prostaglandins, Synthetic - metabolism ; Rats ; Rats, Wistar ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Urinary Bladder - drug effects ; Urinary Bladder - enzymology ; Urinary Bladder - metabolism ; Urination - drug effects</subject><ispartof>American journal of physiology. 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A</creatorcontrib><title>COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat</title><title>American journal of physiology. Regulatory, integrative and comparative physiology</title><addtitle>Am J Physiol Regul Integr Comp Physiol</addtitle><description>Departments of 1  Neurology, 2  Anatomy and Neurobiology, and 3  Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405 The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute (4 h), intermediate (48 h), or chronic (10 day) cyclophosphamide (CYP)-induced cystitis. Bladders were harvested from euthanized female rats for analyses. Conscious cystometry was used to assess the effects of a COX-2-specific inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl2(5 H )-furanone (DFU, 5 mg/kg sc), a disubstituted furanone, in CYP-induced cystitis. COX-2 mRNA was increased in inflamed bladders after acute (12-fold) and chronic (9-fold) treatment. COX-2 protein expression in inflamed bladders paralleled COX-2 mRNA expression. Prostaglandin D 2 -methoxime expression in the bladder was significantly ( P    0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E 2 was significantly ( P    0.01) increased (2-fold) in the bladder with intermediate (1.7-fold) and chronic (2.6-fold) cystitis. COX-2-immunoreactive cell profiles were distributed throughout the inflamed bladder and coexpressed histamine immunoreactivity. Conscious cystometry in rats treated with CYP + DFU showed increased micturition intervals 4 and 48 h after CYP treatment and decreased intravesical pressures during filling and micturition compared with rats treated with CYP + vehicle. These studies suggest an involvement of urinary bladder COX-2 and its metabolites in altered micturition reflexes with CYP-induced cystitis. inflammation; prostaglandins; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5 H )-furanone; mast cells; cystometry</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cyclooxygenase 2</subject><subject>Cyclophosphamide - administration &amp; dosage</subject><subject>Cyclophosphamide - pharmacology</subject><subject>Cystitis - chemically induced</subject><subject>Cystitis - enzymology</subject><subject>Cystitis - metabolism</subject><subject>Cystitis - physiopathology</subject><subject>Dinoprostone - metabolism</subject><subject>Drug Administration Schedule</subject><subject>Female</subject><subject>Furans - pharmacology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Immunoenzyme Techniques</subject><subject>Immunohistochemistry</subject><subject>Isoenzymes - antagonists &amp; inhibitors</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Prostaglandin D2 - analogs &amp; derivatives</subject><subject>Prostaglandin D2 - metabolism</subject><subject>Prostaglandin-Endoperoxide Synthases - genetics</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>Prostaglandins, Synthetic - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Urinary Bladder - drug effects</subject><subject>Urinary Bladder - enzymology</subject><subject>Urinary Bladder - metabolism</subject><subject>Urination - drug effects</subject><issn>0363-6119</issn><issn>1522-1490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kF1LwzAUhoMobk7_gBfSP9CZr3bNpQynwkCQCd6FNE3XjH6EJGXrvzd10115dTic93nhPADcIzhHKMGPYmes2vZzCGmazDGE-AJMwwHHiDJ4CaaQpCROEWITcOPcDoYgoeQaTBAmWUYpnYLd8v0rxpFoi8jYznnRdrqI1CE0O6e7NtJt1Gjpe6v9uBrhq70YXCRKr2wkB1l3puqcqUSjCxXrtuilKsLB-UC4kfeViqzwt-CqFLVTd6c5A5-r583yNV6_v7wtn9axpAnxcZLBJEc4gVnKaJYrVSKZlzClSGAhUSYTJhc5U4TRnGThdQapCoiUC4FYScgM4GOvDA85q0purG6EHTiCfBTHT-L4jzg-igvQwxEyfd6o4oycTIVAfAxUelvttVXcVEMwVHfb4a8QZ5Rj_pEsxjz7P7_q63qjDv4XPHPcFCX5BlMFkmc</recordid><startdate>20030201</startdate><enddate>20030201</enddate><creator>Hu, V. 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A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-5805b125086948beef1cbf0641a2ac18c59c7b9e394b38046904e05bcc7a19f33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cyclooxygenase 2</topic><topic>Cyclophosphamide - administration &amp; dosage</topic><topic>Cyclophosphamide - pharmacology</topic><topic>Cystitis - chemically induced</topic><topic>Cystitis - enzymology</topic><topic>Cystitis - metabolism</topic><topic>Cystitis - physiopathology</topic><topic>Dinoprostone - metabolism</topic><topic>Drug Administration Schedule</topic><topic>Female</topic><topic>Furans - pharmacology</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Immunoenzyme Techniques</topic><topic>Immunohistochemistry</topic><topic>Isoenzymes - antagonists &amp; inhibitors</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Prostaglandin D2 - analogs &amp; derivatives</topic><topic>Prostaglandin D2 - metabolism</topic><topic>Prostaglandin-Endoperoxide Synthases - genetics</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>Prostaglandins, Synthetic - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Urinary Bladder - drug effects</topic><topic>Urinary Bladder - enzymology</topic><topic>Urinary Bladder - metabolism</topic><topic>Urination - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, V. Y</creatorcontrib><creatorcontrib>Malley, S</creatorcontrib><creatorcontrib>Dattilio, A</creatorcontrib><creatorcontrib>Folsom, J. B</creatorcontrib><creatorcontrib>Zvara, P</creatorcontrib><creatorcontrib>Vizzard, M. A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>American journal of physiology. Regulatory, integrative and comparative physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, V. Y</au><au>Malley, S</au><au>Dattilio, A</au><au>Folsom, J. B</au><au>Zvara, P</au><au>Vizzard, M. A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat</atitle><jtitle>American journal of physiology. Regulatory, integrative and comparative physiology</jtitle><addtitle>Am J Physiol Regul Integr Comp Physiol</addtitle><date>2003-02-01</date><risdate>2003</risdate><volume>284</volume><issue>2</issue><spage>574</spage><epage>R585</epage><pages>574-R585</pages><issn>0363-6119</issn><eissn>1522-1490</eissn><abstract>Departments of 1  Neurology, 2  Anatomy and Neurobiology, and 3  Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405 The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute (4 h), intermediate (48 h), or chronic (10 day) cyclophosphamide (CYP)-induced cystitis. Bladders were harvested from euthanized female rats for analyses. Conscious cystometry was used to assess the effects of a COX-2-specific inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl2(5 H )-furanone (DFU, 5 mg/kg sc), a disubstituted furanone, in CYP-induced cystitis. COX-2 mRNA was increased in inflamed bladders after acute (12-fold) and chronic (9-fold) treatment. COX-2 protein expression in inflamed bladders paralleled COX-2 mRNA expression. Prostaglandin D 2 -methoxime expression in the bladder was significantly ( P    0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E 2 was significantly ( P    0.01) increased (2-fold) in the bladder with intermediate (1.7-fold) and chronic (2.6-fold) cystitis. COX-2-immunoreactive cell profiles were distributed throughout the inflamed bladder and coexpressed histamine immunoreactivity. Conscious cystometry in rats treated with CYP + DFU showed increased micturition intervals 4 and 48 h after CYP treatment and decreased intravesical pressures during filling and micturition compared with rats treated with CYP + vehicle. These studies suggest an involvement of urinary bladder COX-2 and its metabolites in altered micturition reflexes with CYP-induced cystitis. inflammation; prostaglandins; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5 H )-furanone; mast cells; cystometry</abstract><cop>United States</cop><pmid>12388444</pmid><doi>10.1152/ajpregu.00465.2002</doi></addata></record>
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subjects Animals
Blotting, Western
Cyclooxygenase 2
Cyclophosphamide - administration & dosage
Cyclophosphamide - pharmacology
Cystitis - chemically induced
Cystitis - enzymology
Cystitis - metabolism
Cystitis - physiopathology
Dinoprostone - metabolism
Drug Administration Schedule
Female
Furans - pharmacology
Gene Expression Regulation - drug effects
Immunoenzyme Techniques
Immunohistochemistry
Isoenzymes - antagonists & inhibitors
Isoenzymes - genetics
Isoenzymes - metabolism
Prostaglandin D2 - analogs & derivatives
Prostaglandin D2 - metabolism
Prostaglandin-Endoperoxide Synthases - genetics
Prostaglandin-Endoperoxide Synthases - metabolism
Prostaglandins, Synthetic - metabolism
Rats
Rats, Wistar
RNA, Messenger - genetics
RNA, Messenger - metabolism
Urinary Bladder - drug effects
Urinary Bladder - enzymology
Urinary Bladder - metabolism
Urination - drug effects
title COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat
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