Abstract
The urothelium and lamina propria (LP) contribute to sensations of bladder fullness by releasing multiple mediators, including prostaglandins (PGs) and adenosine 5'-triphosphate (ATP), that activate or modulate functions of cells throughout the bladder wall. Mediators that are simultaneously released in response to bladder distention likely influence each other's mechanisms of release and action. This study investigated whether PGs could alter the extracellular hydrolysis of ATP by soluble nucleotidases (s-NTDs) released in the LP of nondistended or distended bladders. Using an ex vivo murine detrusor-free bladder model to access the LP during bladder filling and a sensitive HPLC-FLD detection methodology, we evaluated the decrease in ATP and the increase in adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), and adenosine by s-NTDs released in the LP. Endogenous PGE(2) increased the spontaneous but not the distention-induced release of s-NTD via EP2 and EP3 prostanoid receptors, whereas exogenous PGE(2) increased the spontaneous s-NTD release via EP3, EP4, and FP receptors and the distention-induced s-NTD release via EP1-4 and FP receptors. Endogenous PGF(2α), PGD(2), and PGI(2) did not change the s-NTD release. Exogenous PGD(2) increased the spontaneous s-NTD release via DP2 receptors and the distention-induced s-NTD release via DP1 and DP2 receptors. Exogenous PGF(2α) increased the spontaneous but not the distention-induced release of s-NTD via FP receptors. It is possible that higher concentrations of PGE(2), PGF(2α), and PGD(2) (as expected in inflammation, bladder pain syndrome, or overactive bladder) potentiate the release of s-NTDs and the consecutive degradation of ATP as a safeguard mechanism to prevent the development of excessive bladder excitability and overactivity by high amounts of extracellular ATP.