The Use of the Isolated Mouse Whole Bladder for Investigating Bladder Overactivity

• Published in: The Journal of pharmacology and experimental therapeutics 2006-12, Vol.319 (3), p.1386-1394
• Main Authors: Fabiyi, Adebola C, Brading, Alison F
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Anesthetics, Local - pharmacology; Animals; Atropine - pharmacology; Bradykinin - pharmacology; Carbachol - pharmacology; Dose-Response Relationship, Drug; Electric Stimulation; Female; In Vitro Techniques; Mice; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; Muscle, Smooth - drug effects; Muscle, Smooth - innervation; Neurons - physiology; Receptors, Muscarinic - drug effects; Tetrodotoxin - pharmacology; Urinary Bladder - innervation; Urinary Bladder - physiopathology; Urinary Bladder, Overactive - physiopathology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.106.108902

The isolated mouse whole bladder was used to study in vitro bladder overactivity evoked by intramural nerve sensitization with bradykinin, mimicking neurogenic bladder overactivity secondary to bladder inflammation. Intravesical pressure responses to intramural electrical stimulation of intramural nerves were measured under isovolumetric condition. Validation showed that carbachol produced a dose-response curve closely mirroring that observed in the isolated muscle strips and demonstrated the dual nature of electrically evoked neurotransmission, consisting of a cholinergic component largely mediated by M 3 receptors and a purinergic component mediated by P2X receptors. ATP generated a biphasic dose-response curve, suggesting that the P2X receptors may be heterogeneous in distribution. Characterization of bradykinin receptors showed bradykinin to be extremely potent in exciting the bladder, producing a dose-response curve with an EC 50 of 90 nM, and bradykinin also enhanced electrically evoked bladder contractions. These effects were inhibited by the B 2 receptor antagonist HOE 140 ( d -Arg 0 -Arg 1 -Pro 2 -Hyp 3 -Gly 4 -Thi 5 -Ser 6 - d -Tic 7 -Oic 8 -Arg 9 ) but not the B 1 receptor antagonist desArg 10 HOE 140 (H- d -Arf-Arg-Pro-Hyp-Gly-Thi-Ser- d -Tic-Oic-OH) and were also modulated by α,β,methyleneATP. The isolated mouse whole bladder has proved a viable, robust model in which to demonstrate the pharmacological characteristic of the bladder and adds to the repertoire of in vitro tools for investigating potential therapeutic agents.