Guan Na N, Svennersten Karl, de Verdier Petra J, Wiklund N Peter, Gustafsson Lars E
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
J Cell Mol Med. 2017 Feb;21(2):234-243. doi: 10.1111/jcmm.12959. Epub 2016 Sep 23.
The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD actions in guinea pig out-flow region and the distribution of DP /DP receptors. The effects of PGD on urothelium-intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP /DP receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP /DP receptors. PGD in a dose-dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD was equally (trigone) or slightly less potent (urethra) compared with PGE . Expression of DP and DP receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP and DP receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD 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.
近端尿道和膀胱三角区在控尿中发挥着重要作用。我们之前已经表明，前列腺素D（PGD）从豚鼠膀胱尿路上皮/上皮下释放，并且可以抑制逼尿肌收缩反应。我们目前希望研究PGD在豚鼠流出区域的作用以及DP/DP受体的分布。在器官浴实验中研究了PGD对完整尿路上皮的三角区和近端尿道收缩性的影响。通过蛋白质印迹分析DP/DP受体蛋白的表达。免疫组织化学用于鉴定DP/DP受体的分布。PGD以剂量依赖性方式抑制电场刺激（EFS）诱导的三角区收缩，并抑制近端尿道的自发收缩。与前列腺素E（PGE）相比，PGD在抑制三角区收缩方面效果相当，而在抑制近端尿道收缩方面效果略弱。在雄性豚鼠膀胱三角区、颈部和近端尿道中发现了DP和DP受体的表达。在三角区和近端尿道中，DP受体存在于平滑肌细胞膜上，并且在尿路上皮中观察到弱免疫反应性。DP受体在尿路上皮和平滑肌中分布更广泛、较弱且均匀。PGD对豚鼠三角区和近端尿道运动活性的抑制作用与在三角区和近端尿道的尿路上皮和平滑肌细胞中发现DP和DP受体一致，因此PGD可能是膀胱流出区域的调节剂，可能在排尿调节中起作用，并在膀胱过度活动症中发挥作用。
