Receptors involved in the modulation of guinea pig urinary bladder motility by prostaglandin D2.
OBJECTIVE
We have described a urothelium-dependent release of PGD2 -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 PGD2 formation and of its receptors.


METHODS
In the presence of selective DP and TP receptor antagonists alone or combined, PGD2 was applied to urothelium-denuded diclofenac-treated urinary bladder strips mounted in organ baths. Antibodies against PGD2 synthase and DP1 receptors were used with Western blots and for histochemistry.


RESULTS
PGD2 inhibited nerve stimulation -induced contractions in strips of guinea pig urinary bladder with estimated pIC50 of 7.55 ± 0.15 (n = 13), an effect blocked by the DP1 receptor antagonist BW-A868C. After blockade of DP1 receptors, PGD2 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
In guinea pig urinary bladder, the main effect of PGD2 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 PGD2 receptors of the DP1 type. The results are important for our understanding of regulation of bladder motility.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Na N
NN
Guan
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Karl
K
Svennersten
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Petra J
PJ
de Verdier
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
N Peter
NP
Wiklund
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Lars E
LE
Gustafsson
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D005260:Female; D006168:Guinea Pigs; D006827:Hydantoins / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000502:physiology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006827:Hydantoins; D006834:Hydrazines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C058848:BW A868C; C045749:SQ 29548; D015230:Prostaglandin D2