Fig. 5.

A: luminal ATP release was increased in transgenic mice with chronic urothelial overexpression of nerve growth factor (NGF-OE) and decreased with intravesical instillation of the transient receptor potential vanilloid family member 4 (TRPV4) receptor antagonist HC-067047 (1 µM) in NGF-OE and littermate WT mice. NGF-OE mice exhibited significantly (*P ≤ 0.01) increased luminal ATP release at 25 mmHg compared with littermate WT mice that was significantly (*P ≤ 0.01) reduced with intravesical treatment with HC-067047 (1 µM). Luminal ATP release in NGF-OE mice was also significantly (*P ≤ 0.01) reduced with intravesical instillation of the purinergic (P2) receptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid tetrasodium salt (PPADS; 300 µM). Intravesical PPADS (300 µM) in littermate WT mice was without effect on luminal ATP release. B: luminal ATP release was decreased in NGF-OE and littermate WT mice by intravesical instillation of the general secretory inhibitor brefeldin A (BFA; 10 µM) but unaffected by the inhibitory peptide 10Panx (50 µM) to block pannexin-1 channels. Intravesical instillation of BFA (10 µM) significantly (*P ≤ 0.01) reduced luminal ATP release measured at 25 mmHg from littermate WT and NGF-OE mice. No changes in luminal ATP release were observed in littermate WT or NGF-OE mice with intravesical treatment with 10Panx (50 µM). Intravesical instillation with both BFA (10 µM) and 10Panx (50 µM) reduced luminal ATP release to that observed with BFA treatment alone. Values are means ± SE; n = 6–8 for each group.