Prostaglandin D2effects and DP1/DP2receptor distribution in guinea pig urinary bladder out-flow region.
The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD2is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD2actions in guinea pig out-flow region and the distribution of DP1/DP2receptors. The effects of PGD2on urothelium-intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP1/DP2receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP1/DP2receptors. PGD2in a dose-dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD2was equally (trigone) or slightly less potent (urethra) compared with PGE2. Expression of DP1and DP2receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP1receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP2receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD2on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP1and DP2receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD2may 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.
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; D016616:Cryoultramicrotomy; D015232:Dinoprostone / Q000378:metabolism; D004558:Electric Stimulation; D006168:Guinea Pigs; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D014521:Urethra / Q000294:innervation / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
D011982:Receptors, Prostaglandin; D015232:Dinoprostone; D015230:Prostaglandin D2

DP
1
; 
DP
2
; 
PGD
2
; internal urethral sphincter; prostaglandins; proximal urethra; smooth muscle; trigone; urinary tract
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