Intravesical PAC1 Receptor Antagonist, PACAP(6-38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in NGF-OE Mice

Chronic NGF overexpression (OE) in the urothelium, achieved through the use of a highly urothelium-specific uroplakin II promoter, stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency and non-voiding contractions, and referred somatic sensitivity. Additional NGF-mediated pleiotropic changes might contribute to increased voiding frequency and pelvic hypersensitivity in NGF-OE mice such as neuropeptide/receptor systems including PACAP(Adcyap1) and PAC1 receptor (Adcyap1r1). Given the presence of PAC1-immunoreactive fibers and the expression of PAC1 receptor expression in bladder tissues, and PACAP-facilitated detrusor contraction, whether PACAP/receptor signaling contributes to increased voiding frequency and somatic sensitivity was evaluated in NGF-OE mice. Intravesical administration of the PAC1 receptor antagonist, PACAP(6-38) (300 nM), significantly (p ≤ 0.01) increased intercontraction interval (2.0-fold) and void volume (2.5-fold) in NGF-OE mice. Intravesical instillation of PACAP(6-38) also decreased baseline bladder pressure in NGF-OE mice. PACAP(6-38) had no effects on bladder function in WT mice. Intravesical administration of PACAP(6-38) (300 nM) significantly (p ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in WT mice. PACAP/receptor signaling contributes to the increased voiding frequency and pelvic sensitivity observed in NGF-OE mice.

Journal of molecular neuroscience : MN. 2016 May 04 [Epub]

Beatrice M Girard, Susan E Malley, Morgan M Mathews, Victor May, Margaret A Vizzard

Department of Neurological Sciences, College of Medicine, University of Vermont, D405A Given Research Building, Burlington, VT, 05405, USA., Department of Neurological Sciences, College of Medicine, University of Vermont, D405A Given Research Building, Burlington, VT, 05405, USA., Department of Neurological Sciences, College of Medicine, University of Vermont, D405A Given Research Building, Burlington, VT, 05405, USA., Department of Neurological Sciences, College of Medicine, University of Vermont, D405A Given Research Building, Burlington, VT, 05405, USA., Department of Neurological Sciences, College of Medicine, University of Vermont, D405A Given Research Building, Burlington, VT, 05405, USA. .

E-Newsletters

Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.

Subscribe