Region-specific changes in the phosphorylation of ERK1/2 and ERK5 in rat micturition pathways following cyclophosphamide-induced cystitis.
Chronic inflammation of the urinary bladder generates hyperalgesia and allodynia. Growing evidence suggests a role of ERK in mediating somatic and visceral pain processing. In the present studies, we characterized and compared the activation of two ERK isoforms, ERK1/2 and ERK5, in micturition pathways, including the urinary bladder, lumbosacral dorsal root ganglia (DRG), and spinal cord in adult female and male rats before and after cyclophosphamide (CYP)-induced bladder inflammation. Results showed differential activation of ERK1/2 and ERK5 in these regions following cystitis. The level of phospho-ERK1/2 but not phospho-ERK5 was increased in the urinary bladder; the level of phospho-ERK5 but not phospho-ERK1/2 was increased in DRG; and the level of phospho-ERK1/2 but not phospho-ERK5 was increased in lumbar spinal cord following cystitis compared with control. Cystitis-induced upregulation of phospho-ERK1/2 and phospho-ERK5 was time dependent and showed similar patterns in female and male rats. The level of phospho-ERK1/2 in bladder was increased at 2 and 8 h after CYP injection; the level of phospho-ERK5 in DRG was increased at 8 and 48 h after CYP injection; and the level of phospho-ERK1/2 in lumbar spinal cord was increased at 48 h after CYP injection. The result that phospho-ERK5 was exclusively increased in DRG neurons, while phospho-ERK1/2 was increased in the spinal cord and the urinary bladder after cystitis, suggests a region-specific effect of neurotrophins on micturition pathways following bladder inflammation.
Qiao
Li-Ya
LY
Department of Physiology, Box 980551, Virginia Commonwealth University, Richmond, VA 23298-0551, USA. lqiao2@vcu.edu
Gulick
Melisa A
MA
D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D005727:Ganglia, Spinal / Q000201:enzymology / Q000378:metabolism; D007249:Inflammation; D007274:Injections, Intraperitoneal; D008161:Lumbosacral Region; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D001743:Urinary Bladder / Q000201:enzymology / Q000294:innervation / Q000378:metabolism; D014554:Urination / Q000502:physiology*
D020033:Protein Isoforms; D003520:Cyclophosphamide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048054:Mitogen-Activated Protein Kinase 7