Ex vivo modulation of muscarinically induced contractions by PGE2 and an EP1 receptor antagonist in the guinea pig urinary bladder

OBJECTIVE: Mechanical and physical stimuli can evoke release of several substances by the urothelium, for example, prostaglandin E2 (PGE2), nitric oxide, acetylcholine and adenosine triphosphate. It has been shown, that PGE2 and acetylcholine seem to act in a positive feedback on molecular level. This feedback was located in the urothelial/ suburothelial layer. Therefore, the aim of our study was to investigate the role of PGE2 and one of its receptors, EP1, on muscarinic induced contractions. METHODS: The urethra and bladder of 24 male guinea pigs were dissected after sacrifice of the animal. The bladder was catheterized transurethrally and placed into a preheated organ bath filled with Krebs buffer. The bladders were repeatedly stimulated with the muscarinic agonist arecaidine alone or in combination with a) acetylsalicylic acid, b) PGE2 or c) the EP1 antagonist ONO-8713. All drugs were applied at the serosal side of the bladder. Intravesical pressure was measured and amplitude and frequency of the arecaidine induced response were analyzed. RESULTS: Adding PGE2 before muscarinic stimulations induced an amplifying effect on muscarinically induced contractions and inhibition of the PGE2 producing enzymes prior to an arecaidine stimulation decreased the amplitude during the initial phase of the response. Inhibition of EP1 resulted in a decreased frequency during the second phase of the arecaidine response. CONCLUSIONS: In summary, this study provides evidence that the cholinergic and prostanoid systems in the urinary bladder act in a positive feedback loop and that the EP1 receptor plays a subtle role in this process.