Premium
Receptors involved in the modulation of guinea pig urinary bladder motility by prostaglandin D 2
Author(s) -
Guan,
Svennersten Karl,
Verdier Petra J,
Wiklund N Peter,
Gustafsson Lars E
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13174
Subject(s) - urothelium , receptor , urinary bladder , endocrinology , medicine , interstitial cell of cajal , biology , receptor antagonist , purinergic receptor , stimulation , motility , tachykinin receptor , urinary bladder disease , chemistry , antagonist , urinary system , microbiology and biotechnology , neuropeptide , substance p , smooth muscle
Background and Purpose We 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 Approach In 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 DP 1 receptors were used with Western blots and for histochemistry. Key Results PGD 2 inhibited nerve stimulation ‐induced contractions in strips of guinea pig urinary bladder with estimated p IC 50 of 7.55 ± 0.15 ( n = 13), an effect blocked by the DP 1 receptor antagonist BW ‐ A 868 C . After blockade of DP 1 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 DP 1 receptors were found in the smooth muscle of the bladder wall with a dominant localization to smooth muscle membranes. Conclusions and Implications In guinea pig urinary bladder, the main effect of PGD 2 is an inhibitory action via DP 1 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 DP 1 type. The results are important for our understanding of regulation of bladder motility.