Center for Translational Medicine at the Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States.
Department of Neurology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States.
Am J Physiol Regul Integr Comp Physiol. 2023 Oct 1;325(4):R344-R358. doi: 10.1152/ajpregu.00273.2022. Epub 2023 Jul 17.
Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6-21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9-13 mo, then reinnervated with 8-12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined. Strip response to epibatidine, expressed as percent potassium chloride, was similar (∼35% in controls, 30% in Decentralized, and 24% in ObNT-Reinn). Differentially, epibatidine responses in Decentralized and ObNT-Reinn bladder strips were lower than controls after tetrodotoxin (TTX, a sodium channel blocker that inhibits axonal action potentials). Yet, in all groups, epibatidine-induced strip contractions were similarly inhibited by mecamylamine and hexamethonium (ganglionic nicotinic receptor antagonists), SR 16584 (α3β4 neuronal nicotinic receptor antagonist), atracurium and tubocurarine (neuromuscular nicotinic receptor antagonists), and atropine (muscarinic receptor antagonist), indicating that nicotinic receptors (particularly α3β4 subtypes), neuromuscular and muscarinic receptors play roles in bladder contractility. In control bladder strips, since tetrodotoxin did not inhibit epibatidine contractions, nicotinic receptors are likely located on nerve terminals. The tetrodotoxin inhibition of epibatidine-induced contractions in Decentralized and ObNT-Reinn suggests a relocation of nicotinic receptors from nerve terminals to more distant axonal sites, perhaps as a compensatory mechanism to recover bladder function.
目前对于犬类膀胱中烟碱型乙酰胆碱受体的生理功能知之甚少，尽管在许多物种的膀胱中已报道存在功能性烟碱型乙酰胆碱受体。本研究采用体外方法评估了介导犬类膀胱功能的烟碱型乙酰胆碱受体：对照组（9 名雌性和 11 名雄性正常对照，5 名假手术）、去神经支配组（9 名雌性，去神经支配 6-21 个月）和闭孔神经-骨盆神经转位再支配组（ObNT-Reinn；9 名雌性；去神经支配 9-13 个月，然后再支配 8-12 个月恢复）。在孵育神经递质拮抗剂之前，收集肌条、去除黏膜并安装在肌浴槽中，然后测定烟碱型乙酰胆碱受体激动剂 epibatidine 的收缩反应。epibatidine 引起的肌条反应（以氯化钾百分比表示）在对照组中相似（约 35%，在去神经支配组中为 30%，在 ObNT-Reinn 组中为 24%）。不同的是，在去神经支配组和 ObNT-Reinn 组的 epibatidine 反应在河豚毒素（TTX，一种抑制轴突动作电位的钠离子通道阻滞剂）处理后低于对照组。然而，在所有组中，epibatidine 诱导的肌条收缩均被美加明和六烃季铵（烟碱型乙酰胆碱受体拮抗剂）、SR 16584（α3β4 神经元烟碱型乙酰胆碱受体拮抗剂）、阿曲库铵和筒箭毒碱（神经肌肉烟碱型乙酰胆碱受体拮抗剂）和阿托品（毒蕈碱受体拮抗剂）类似抑制，表明烟碱型乙酰胆碱受体（特别是α3β4 亚型）、神经肌肉和毒蕈碱受体在膀胱收缩中起作用。在对照组的膀胱肌条中，由于河豚毒素不抑制 epibatidine 收缩，因此烟碱型乙酰胆碱受体可能位于神经末梢。河豚毒素抑制去神经支配组和 ObNT-Reinn 组中 epibatidine 诱导的收缩表明烟碱型乙酰胆碱受体从神经末梢重新定位到更远的轴突部位，这可能是一种恢复膀胱功能的代偿机制。
