While acetylcholine is regarded to be the main directly contractile transmitter substance in the urinary bladder, interactions with other transmitters likely occur. Presently, the interplay between purinergic and cholinergic signalling was investigated to unravel the involvement of the urothelium and efferent neurons in the functionally important purinergically evoked release of acetylcholine in vitro. Functional characterization of receptor subtypes involved in this interplay was also performed. In vitro organ bath experiments with electrical field stimulation (EFS) or administration of agonist were performed in the absence and presence of the neurotoxin tetrodotoxin (TTX; 5 × 10-7 M) and/or receptor antagonists, in intact and urothelium-denuded full thickness rat bladder strip preparations. Interestingly, functional contractions to ATP (10-6-10-3 M) remained unaffected by TTX, but were significantly lowered in the presence of the muscarinic antagonist atropine (10-6 M). However, in urothelium-denuded strip preparations, this latter phenomenon was not present and the ATP response remained unaltered. To rule out purinergic interference caused by break-down of ATP, experiments were performed in which the stable ATP-analogue αβMeATP (10-7-10-5 M) gave rise to functional atropine-sensitive contractions. Furthermore, contractions to ATP were not affected by P2Y6 purinoceptor blockade (by MRS2578; 10-7, 10-5 M), nor were relaxatory responses to ATP sensitive to atropine, PPADS (3 × 10-5 M) or αβMeATP. Lastly, relaxations to ADP (10-6-10-3 M) or NECA (10-8-10-5 M) were unaltered by the presence of atropine. To conclude, purinergic functional contractile, but not relaxatory, responses are supported by the cholinergic transmitter system in vitro, through non-neuronal mechanisms in the urothelium. Involved purinoceptors are of the P2X-subtype, most likely P2X1 and/or P2X3.

中文翻译：

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健康大鼠膀胱中的功能性阿托品敏感嘌呤能反应

虽然乙酰胆碱被认为是膀胱中主要的直接收缩性递质物质，但可能会发生与其他递质的相互作用。目前，研究了嘌呤能和胆碱能信号之间的相互作用，以解开尿路上皮和传出神经元在体外乙酰胆碱的重要嘌呤能诱发释放中的参与。还进行了参与这种相互作用的受体亚型的功能表征。在神经毒素河豚毒素 (TTX; 5 × 10-7 M) 和/或受体拮抗剂不存在和存在的情况下，在完整和脱去尿路上皮的完整细胞中进行电场刺激 (EFS) 或激动剂给药的体外器官浴实验。厚大鼠膀胱条制剂。有趣的是，ATP (10-6-10-3 M) 的功能性收缩不受 TTX 影响，但在毒蕈碱拮抗剂阿托品 (10-6 M) 存在下显着降低。然而，在去除尿路上皮的条带制剂中，后一种现象不存在，ATP 反应保持不变。为了排除由 ATP 分解引起的嘌呤能干扰，进行了实验，其中稳定的 ATP 类似物 αβMeATP (10-7-10-5 M) 引起功能性阿托品敏感收缩。此外，对 ATP 的收缩不受 P2Y6 嘌呤受体阻断（通过 MRS2578；10-7、10-5 M）的影响，对阿托品、PPADS（3 × 10-5 M）或 αβMeATP 敏感的 ATP 的松弛反应也不受影响。最后，阿托品的存在未改变对 ADP (10-6-10-3 M) 或 NECA (10-8-10-5 M) 的松弛。总之，嘌呤能功能收缩，体外胆碱能递质系统通过尿路上皮中的非神经元机制支持反应，但不是松弛反应。参与的嘌呤受体属于 P2X 亚型，最有可能是 P2X1 和/或 P2X3。