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1 Neurology, University of Vermont, Burlington, United States
2 Neurology, University of Vermont, Burlington, United States; Anatomy and Neurobiology, University of Vermont, Burlington, United States
* To whom correspondence should be addressed. E-mail: margaret.vizzard{at}uvm.edu.
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 hr, 48 hr or chronic) in rats. The expression of CRF receptors, CRF1 and CRF2, was examined in urinary bladder from control and CYP-treated rats. Urinary bladder and lumbosacral spinal cord were harvested from rats euthanized by isoflurane (4%) and thoracotomy. CRF protein expression in whole urinary bladders significantly (p 
0.01) increased with 48 hr or chronic CYP treatment. CRF-immunoreactivity (IR) was significantly (p 0.01) increased 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. CRF2 receptor transcript was expressed in the urothelium or detrusor smooth muscle and CRF2 receptor expression increased in whole bladder with CYP-treatment whereas no CRF1 receptor transcript was expressed in either urothelium or detrusor. Immunohistochemical studies demonstrated CRF2-IR in urinary bladder nerve fibers and urothelial cells from control animals whereas no CRF1-IR was observed. These studies demonstrated changes in the expression CRF in urinary bladder and SPN region with CYP-induced cystitis and CRF receptor (CRF2) expression in nerve fibers and urothelium in control rats. CRF may contribute to urinary bladder overactivity and altered sensory processing with CYP-induced cystitis.
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