The use of the isolated mouse whole bladder for investigating bladder overactivity
The use of the isolated mouse whole bladder for investigating bladder overactivity
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DOI：
10.1124/jpet.106.108902
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发表时间：
2006-12-01
影响因子：
3.5
通讯作者：
Brading, Alison F.
中科院分区：
文献类型：
--
作者：
Fabiyi, Adebola C.;Brading, Alison F.
使用分离的小鼠整个膀胱来研究由缓激肽的壁内神经敏化引起的体外膀胱过度活动，模拟继发于膀胱炎症的神经源性膀胱过度活动。在等容条件下测量对壁内神经的壁内电刺激的膀胱内压力反应。验证表明，卡巴胆碱产生的剂量反应曲线与在分离的肌肉条中观察到的密切相关，并证明了电诱发神经传递的双重性质，包括主要由 M-3 受体介导的胆碱能成分和由 P2X 受体介导的嘌呤能成分。 ATP 产生双相剂量反应曲线，表明 P2X 受体的分布可能是异质的。缓激肽受体的表征表明，缓激肽在刺激膀胱方面非常有效，产生 EC50 为 90 nM 的剂量反应曲线，并且缓激肽还可以增强电诱发的膀胱收缩。 B-2 受体拮抗剂 HOE 140(D-Arg(0)-Arg(1)-Pro(2)-Hyp(3)-Gly(4)-Thi(5)-Ser(6)-D-Tic(7)Oic(8)-Arg(9)) 可抑制这些作用，但 B 1 受体拮抗剂 desArg(10) HOE 140 不会抑制这些作用(H-D-Arf-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-OH) 也受到 α、β、亚甲基 ATP 的调节。分离的小鼠整个膀胱已被证明是一种可行、稳健的模型，可以证明膀胱的药理学特征，并增加了用于研究潜在治疗剂的体外工具库。
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 EC50 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 alpha,beta,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.