Release and inhibitory effects of prostaglandin D2 in guinea pig urinary bladder and the role of urothelium.

BACKGROUND

While studying a urothelium-derived inhibitory factor in guinea pig urinary bladders we observed considerable release of prostanoids, including PGD2-like activity. The present study was carried out to identify the prostanoids and to study their roles in modulating guinea pig urinary bladder motility.

METHODS

Release of PGE2 and PGD2 in isolated guinea pig urinary bladder preparations was analyzed by high performance liquid chromatography (HPLC) combined with bioassay on bladder strips. Isolated urothelium-intact (UI) or -denuded (UD) bladder strips were subjected to electrical field stimulation (EFS) and applications of PGE2 and PGD2.

RESULTS

A resting release of 95±9 (n=5) nggtissue(-1)h(-1) PGE2-like activity and 210±34 (n=4) nggtissue(-1)h(-1) PGD2-like activity was found, where PGD2-like was subject to marked spontaneous inactivation during isolation. Prostanoids release was decreased by 70-90% by the cyclo-oxygenase inhibitor diclofenac in UI preparations. Urothelium removal decreased prostanoids release by more than 90%. PGE2 increased basal tone and spontaneous contractions, whereas PGD2 had little or no effect on these. Exogenous PGE2 enhanced and PGD2 inhibited contractile responses to EFS, exogenous acetylcholine- and ATP, whereas PGD2 caused marked dose-dependent inhibition. PGE2 and PGD2 effects were more pronounced in diclofenac-treated UD tissues.

CONCLUSIONS

PGD2 and PGE2 are released from guinea pig bladder urothelium and PGD2 has inhibitory effects on bladder motility, mainly through a postjunctional action on smooth muscle responsiveness.

GENERAL SIGNIFICANCE

The release and inhibitory effects merit further studies in relation to normal biological function as well as overactive bladder syndrome.