Prostaglandin D₂ effects and DP₁ /DP₂ receptor distribution in guinea pig urinary bladder out-flow region

The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD₂ is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD₂ actions in guinea pig out-flow region and the distribution of DP₁ /DP₂ receptors. The effects of PGD₂ on urothelium-intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP₁ /DP₂ receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP₁ /DP₂ receptors. PGD₂ in a dose-dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD₂ was equally (trigone) or slightly less potent (urethra) compared with PGE₂ . Expression of DP₁ and DP₂ receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP₁ receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP₂ receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD₂ on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP₁ and DP₂ receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD₂ may therefore be a modulator of the bladder out-flow region, possibly having a function in regulation of micturition and a role in overactive bladder syndrome.