COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat.
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(5H)-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 D2-methoxime expression in the bladder was significantly (P < or = 0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E2 was significantly (P < or = 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.
Hu
V Y
VY
Departments of Neurology, Anatomy and Neurobiology, and Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Malley
S
S
Dattilio
A
A
Folsom
J B
JB
Zvara
P
P
Vizzard
M A
MA
D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D003556:Cystitis / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D015232:Dinoprostone / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D005663:Furans / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011465:Prostaglandins, Synthetic / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014554:Urination / Q000187:drug effects*
C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D005663:Furans; D007527:Isoenzymes; D011465:Prostaglandins, Synthetic; D012333:RNA, Messenger; C048156:11-methoxime prostaglandin D2; D003520:Cyclophosphamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2