Mechanical stretch of the urothelium induces the release of ATP that activates bladder afferent nerves. In the rat urinary bladder, ATP is also a contractile co-transmitter in the parasympathetic innervation. In isolated preparations, ATP evokes a urothelial release of acetylcholine that substantially contributes to ATP-evoked contractile responses. Currently we aimed to further examine the interactions of ATP and acetylcholine in the rat urinary bladder in two in vivo models. In the whole bladder preparation, atropine reduced ATP-evoked responses by about 50% in intact but denervated bladders, while atropine had no effect after denudation of the urothelium. In a split bladder preparation, reflex-evoked responses of the contralateral half were studied by applying stimuli (agonists or stretch) to the ipsilateral half. Topical administration of ATP and methacholine as well as of stretch induced contralateral reflex-evoked contractions. While topical administration of atropine ipsilaterally reduced the ATP- and stretch-induced contralateral contractions by 27 and 39%, respectively, the P2X purinoceptor antagonist PPADS reduced them by 74 and 84%. In contrary, the muscarinic M2-(M4)-selective receptor antagonist methoctramine increased the responses by 38% (ATP) and 75% (stretch). Pirenzepine (M1-selective antagonist) had no effect on the reflex. In vitro, in the absence of the reflex, methoctramine did not affect the ATP-induced responses. It is concluded that urothelial ATP potently induces the micturition reflex and stimulates urothelial release of acetylcholine. Acetylcholine subsequently acts on afferents and on the detrusor muscle. While muscarinic M2 and/or M4 receptors in the sensory innervation exert inhibitory modulation, muscarinic M3 receptors cause excitation.

中文翻译：

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ATP 诱导的尿路上皮乙酰胆碱在大鼠膀胱中的体内旁分泌作用

尿路上皮的机械拉伸诱导激活膀胱传入神经的 ATP 的释放。在大鼠膀胱中，ATP 也是副交感神经支配中的收缩性共递质。在分离的制剂中，ATP 引起尿路上皮释放乙酰胆碱，这对 ATP 引起的收缩反应有很大贡献。目前，我们旨在在两个体内模型中进一步检查 ATP 和乙酰胆碱在大鼠膀胱中的相互作用。在整个膀胱制备中，阿托品使完整但去神经支配的膀胱中 ATP 诱发的反应降低了约 50%，而阿托品在去除尿路上皮后没有影响。在分裂膀胱准备中，通过对同侧半部施加刺激（激动剂或拉伸）来研究对侧半部的反射诱发反应。ATP 和乙酰甲胆碱的局部给药以及拉伸引起的对侧反射诱发的收缩。虽然阿托品的局部给药使 ATP 和牵张诱导的对侧收缩分别减少了 27% 和 39%，但 P2X 嘌呤受体拮抗剂 PPADS 将它们减少了 74% 和 84%。相反，毒蕈碱 M2-(M4) 选择性受体拮抗剂甲氨蝶呤将反应提高了 38% (ATP) 和 75% (拉伸)。哌仑西平（M1 选择性拮抗剂）对反射没有影响。在体外，在没有反射的情况下，甲氨蝶呤不影响 ATP 诱导的反应。结论是尿路上皮 ATP 有效诱导排尿反射并刺激尿路上皮释放乙酰胆碱。乙酰胆碱随后作用于传入神经和逼尿肌。