Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Brain Res Bull. 2011 Aug 10;86(1-2):91-6. doi: 10.1016/j.brainresbull.2011.06.001. Epub 2011 Jun 13.
The purpose of this study was to examine the pharmacologic plasticity of cholinergic, non-adrenergic non-cholinergic (NANC), and purinergic contractions in neurogenic bladder strips from spinal cord injured (SCI) rats. Bladder strips were harvested from female rats three to four weeks after T(9)-T(10) spinal cord transection. The strips were electrically stimulated using two experimental protocols to compare the contribution of muscarinic and NANC/purinergic contractions in the presence and the absence of carbachol or muscarine. The endpoints of the study were: (1) percent NANC contraction that was unmasked by the muscarinic antagonist 4-DAMP, and (2) P2X purinergic contraction that was evoked by α,β-methylene ATP. NANC contraction accounted for 78.5% of the neurally evoked contraction in SCI bladders. When SCI bladder strips were treated with carbachol (10 μM) prior to 4-DAMP (500 nM), the percent NANC contraction decreased dramatically to only 13.1% of the neurally evoked contraction (P=0.041). This was accompanied by a substantial decrease in α,β-methylene ATP evoked P2X contraction, and desensitization of purinergic receptors (the ratio of subsequent over initial P2X contraction decreased from 97.2% to 42.1%, P=0.0017). Sequential activation of the cholinergic receptors with carbachol (or with muscarine in neurally intact bladders) and unmasking of the NANC response with 4-DAMP switched the neurally evoked bladder contraction from predominantly NANC to predominantly cholinergic. We conclude that activation of muscarinic receptors (with carbachol or muscarine) blocks NANC and purinergic contractions in neurally intact or in SCI rat bladders. The carbachol-induced inhibition of the NANC contraction is expressed more in SCI bladders compared to neurally intact bladders. Along with receptor plasticity, this change in bladder function may involve P2X-independent mechanisms.
本研究旨在探讨脊髓损伤（SCI）大鼠神经源性膀胱条中胆碱能、非肾上腺素能非胆碱能（NANC）和嘌呤能收缩的药理可塑性。在 T（9）-T（10）脊髓横断后 3 至 4 周，从雌性大鼠中采集膀胱条。使用两种实验方案对条带进行电刺激，以比较在存在和不存在卡巴胆碱或毒蕈碱的情况下，毒蕈碱和 NANC/嘌呤能收缩的贡献。研究的终点是：（1）被毒蕈碱拮抗剂 4-DAMP 揭示的 NANC 收缩百分比，和（2）由α，β-亚甲基 ATP 引发的 P2X 嘌呤能收缩。NANC 收缩占 SCI 膀胱神经诱发收缩的 78.5%。当 SCI 膀胱条用卡巴胆碱（10 μM）预处理后再用 4-DAMP（500 nM）处理时，NANC 收缩百分比急剧下降至仅为神经诱发收缩的 13.1%（P=0.041）。这伴随着α，β-亚甲基 ATP 诱发的 P2X 收缩的显著减少，以及嘌呤能受体的脱敏（后续与初始 P2X 收缩的比值从 97.2%降至 42.1%，P=0.0017）。用卡巴胆碱（或在神经完整的膀胱中用毒蕈碱）顺序激活胆碱能受体并用 4-DAMP 揭示 NANC 反应，将神经诱发的膀胱收缩从主要是 NANC 转换为主要是胆碱能。我们得出结论，激活毒蕈碱受体（用卡巴胆碱或毒蕈碱）可阻断神经完整或 SCI 大鼠膀胱中的 NANC 和嘌呤能收缩。与神经完整的膀胱相比，SCI 膀胱中卡巴胆碱诱导的 NANC 收缩抑制更为明显。除了受体可塑性之外，这种膀胱功能的变化可能涉及 P2X 非依赖性机制。
