Abstract
The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD 2 is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD 2 actions in guinea pig out‐flow region and the distribution of DP 1/DP 2 receptors. The effects of PGD 2 on urothelium‐intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP 1/DP 2 receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP 1/DP 2 receptors. PGD 2 in a dose‐dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD 2 was equally (trigone) or slightly less potent (urethra) compared with PGE 2. Expression of DP 1 and DP 2 receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP 1 receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP 2 receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD 2 on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP 1 and DP 2 receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD 2 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.
Highlights
The lower urinary tract (LUT) consists of the urinary bladder and the urethra with the functions of urine storage and periodic urination
We have previously shown that PGD2 and PGE2 were released from guinea pig urinary bladder and that PGD2 inhibited induced bladder detrusor contractions [10]
Strips of proximal urethra taken below the bladder neck and above the duct openings, representing the major region of the internal urethral sphincter (IUS), showed regular, slow and long-lasting (30– 40 sec.) spontaneous contractions (Fig. 1)
Summary
The lower urinary tract (LUT) consists of the urinary bladder and the urethra with the functions of urine storage and periodic urination. Continence and micturition involve a balance between detrusor activity and urethral sphincter closure. Bladder filling and voiding are controlled by a complex pattern of afferent and efferent signalling in parasympathetic, sympathetic and somatic pathways [1, 2]. In addition to neural control, other mediators including prostaglandins are involved in this process. Expression of cyclo-oxygenase in the urinary bladder has been found [3]. Production of prostaglandins locally within the urinary tract in human and other species has been well-studied. Disturbed release of inhibitory and excitatory factors
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