Receptors involved in the modulation of guinea pig urinary bladder motility by prostaglandin D2

Background and PurposeWe have described a urothelium-dependent release of PGD(2)-like activity which had inhibitory effects on the motility of guinea pig urinary bladder. Here, we have pharmacologically characterized the receptors involved and localized the sites of PGD(2) formation and of its receptors. Experimental ApproachIn the presence of selective DP and TP receptor antagonists alone or combined, PGD(2) was applied to urothelium-denuded diclofenac-treated urinary bladder strips mounted in organ baths. Antibodies against PGD(2) synthase and DP1 receptors were used with Western blots and for histochemistry. Key ResultsPGD(2) inhibited nerve stimulation -induced contractions in strips of guinea pig urinary bladder with estimated pIC(50) of 7.55 0.15 (n = 13), an effect blocked by the DP1 receptor antagonist BW-A868C. After blockade of DP1 receptors, PGD(2) enhanced the contractions, an effect abolished by the TP receptor antagonist SQ-29548. Histochemistry revealed strong immunoreactivity for PGD synthase in the urothelium/suburothelium with strongest reaction in the suburothelium. Immunoreactive DP1 receptors were found in the smooth muscle of the bladder wall with a dominant localization to smooth muscle membranes. Conclusions and ImplicationsIn guinea pig urinary bladder, the main effect of PGD(2) is an inhibitory action via DP1 receptors localized to the smooth muscle, but an excitatory effect via TP receptors can also be evoked. The urothelium with its suburothelium might signal to the smooth muscle which is rich in PGD(2) receptors of the DP1 type. The results are important for our understanding of regulation of bladder motility.