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Targeting PACAP Shows Promise in Study of Mice with Bladder Dysfunction

Girard BM, Malley SE, Mathews MM, May V, Vizzard MA. Intravesical PAC1 Receptor Antagonist, PACAP(6-38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in NGF-OE Mice. J Mol Neurosci. 2016 May 4. [Epub ahead of print] At one time, investigators had analyzed compounds called pituitary adenylate cyclase activating polypeptide (PACAP) analogs for their potential anti-cancer effects. They found that one in particular, known as PACAP(6-38), significantly slowed growth of human prostate cancer and breast cancer tumor cells implanted into mice, suggesting PACAP receptors were present on the cancer cells and could be targeted for treatment using this compound. Subsequently, it was reported that PACAP is upregulated in the bladder after chronic cystitis, contributing to bladder contractility and urination reflex in mice. In the present study, a group of researchers has found that the PACAP(6-38) compound improves pelvic sensitivity and decreases urinary bladder frequency in mice with induced urologic dysfunction. By giving PACAP(6-38) to these mice intravesically (i.e., directly to the bladder via a catheter), the researchers were able to demonstrate a significant increase in voiding volume and in the time interval between contractions, along with a decrease in bladder pressure. By contrast, the compound showed no impact on bladder function when given to normal mice. These findings suggest that signaling of PACAP receptors contributes to bladder dysfunction in mice, which means that agents such as PACAP(6-38) might deserve further study in this setting.

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