Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis

Departments of 2 Anatomy and Neurobiology and 1 Neurology, University of Vermont College of Medicine, Burlington, Vermont Submitted 1 February 2006 ; accepted in final form 4 April 2006 Corticotropin-releasing factor (CRF) is a prominent neuropeptide involved in micturition reflexes, and different roles in these reflexes have been suggested. These studies examined the expression of CRF in the urinary bladder and lumbosacral sacral parasympathetic nucleus (SPN) in response to cyclophosphamide (CYP)-induced cystitis (4 h, 48 h, or chronic) in rats. The expression of CRF receptors, CRF 1 and CRF 2 , was examined in urinary bladder from control and CYP-treated rats. Urinary bladder and lumbosacral spinal cord were harvested from rats killed by isoflurane (4%) and thoracotomy. CRF protein expression in whole urinary bladders significantly ( P 0.01) increased with 48 h or chronic CYP treatment. CRF immunoreactivity (IR) was increased significantly ( P 0.01) in the urothelium and SPN after CYP treatment. CRF IR nerve fibers increased in density in the suburothelial plexus and detrusor smooth muscle whole mounts with CYP-induced cystitis. CRF 2 receptor transcript was expressed in the urothelium or detrusor smooth muscle, and CRF 2 receptor expression increased in whole bladder with CYP-treatment, whereas no CRF 1 receptor transcript was expressed in either urothelium or detrusor. Immunohistochemical studies demonstrated CRF 2 IR in urinary bladder nerve fibers and urothelial cells from control animals, whereas no CRF 1 IR was observed. These studies demonstrated changes in the expression of CRF in urinary bladder and SPN region with CYP-induced cystitis and CRF receptor (CRF 2 ) expression in nerve fibers and urothelium in control rats. CRF may contribute to urinary bladder overactivity and altered sensory processing with CYP-induced cystitis. inflammation; sacral parasympathetic nucleus; urothelium; enzyme-linked immunosorbet assay Address for reprint requests and other correspondence: M. A. Vizzard, Dept. of Neurology, Univ. of Vermont College of Medicine, D411 Given Bldg., Burlington, VT 05405 (e-mail: margaret.vizzard{at}uvm.edu )