Phosphorylation of extracellular signal-regulated kinases in urinary bladder in rats with cyclophosphamide-induced cystitis.
Phosphorylated ERK expression has been demonstrated in the central and peripheral nervous system after various stimuli, including visceral stimulation. Changes in the activation (i.e., phosphorylation) of extracellular signal-regulated kinases (pERK) were examined in the urinary bladder after 4 h (acute), 48 h (intermediate), or chronic (10 day) cyclophosphamide (CYP) treatment. CYP-induced cystitis significantly (P < or = 0.01) increased pERK expression in the urinary bladder with intermediate (48 h) and chronic CYP treatment. Immunohistochemistry for pERK immunoreactivity revealed little pERK-IR in control or acute (4 h) CYP-treated rat urinary bladders. However, pERK expression was significantly (P < or = 0.01) upregulated in the urothelium after 48 h or chronic CYP treatment. Whole mount preparations of urothelium/lamina propria or detrusor smooth muscle from control (noninflamed) rats showed no pERK-IR in PGP9.5-labeled nerve fibers in the suburothelial plexus. However, with CYP-treatment (48 h, chronic), a few pERK-IR nerve fibers in the suburothelial plexus of whole mount preparations of bladder and at the serosal edge of urinary bladder sections were observed. pERK-IR cells expressing the CD86 antigen were also observed in urinary bladder from CYP-treated rats (48 h, chronic). Treatment with the upstream inhibitor of ERK phosphorylation, U0126, significantly (P < or= 0.01) increased bladder capacity in CYP-treated rats (48 h). These studies suggest that therapies targeted at pERK pathways may improve urinary bladder function in CYP-treated rats.
Corrow
Kimberly A
KA
Department of Neurology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Vizzard
Margaret A
MA
D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009412:Nerve Fibers / Q000201:enzymology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000502:physiology; D001743:Urinary Bladder / Q000201:enzymology* / Q000294:innervation; D014546:Urinary Catheterization; D019459:Urothelium / Q000201:enzymology
D018906:Antineoplastic Agents, Alkylating; D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D003520:Cyclophosphamide; D048049:Extracellular Signal-Regulated MAP Kinases