Gillespie J I
The Urophysiology Research Group, School of Surgical and Reproductive Sciences, The Medical School, The University of Newcastle upon Tyne, UK.
BJU Int. 2004 Feb;93(3):393-400. doi: 10.1111/j.1464-410x.2003.04624.x.
To investigate the actions of the nonhydrolysable analogue of ATP, alpha,beta-methylene ATP (alpha,beta-MATP) and the sensory peptide, substance P, on the phasic activity generated by muscarinic stimulation in the isolated whole bladder. Isolated bladder can generate complex contractions resulting in phasic rises in intravesical pressure (the autonomous bladder): activity thought to underlie nonmicturition activity in vivo and which may be important in generating bladder sensations.
Experiments were conducted on whole isolated bladders from female guinea pigs (270-300 g). Bladders were cannulated via the urethra, suspended in a heated chamber containing oxygenated solution at 33-36 degrees C and intravesical pressure recorded. All drugs were added to the solution bathing the abluminal surface of the bladder.
When alpha,beta-MATP (30-3000 nmol/L) or substance P (30-300 nmol/L) was added to resting bladders there were small rises in intravesical pressure (<2 cmH2O). However, in the presence of phasic activity generated by exposing the bladder to the muscarinic agonist arecaidine (100-300 nmol/L) or the nicotinic ligand lobeline (10-30 micromol/L) similar or lower concentrations of alpha,beta-MATP or substance P produced more dramatic effects: alpha,beta-MATP and substance P (both at 100 nmol/L) activated a rise in basal pressure of > 15 cmH2O and increased the frequency of the phasic activity. On removing alpha,beta-MATP or substance P, there was a slowing of phasic activity indicative of an inhibitory mechanism.
In addition to direct effects on smooth muscle the agonists alpha,beta-MATP and substance P appear to be potent regulators of the mechanisms generating phasic activity. A developing concept is that the mechanisms responsible for generating phasic activity underlie nonmicturition activity are the target for excitatory and inhibitory inputs. Regulating such activity may be a factor in generating or modifying bladder sensation. Inappropriate or exaggerated phasic activity could underpin the pathological changes which cause the overactive bladder, thus adding another hypothesis to the neurogenic and myogenic hypotheses of bladder overactivity, i.e. that of the autonomous bladder.
研究三磷酸腺苷（ATP）的不可水解类似物α,β-亚甲基三磷酸腺苷（α,β-MATP）和感觉肽P物质对离体完整膀胱中由毒蕈碱刺激产生的时相性活动的作用。离体膀胱可产生复杂收缩，导致膀胱内压出现时相性升高（自主性膀胱）：这种活动被认为是体内非排尿活动的基础，且可能在产生膀胱感觉方面起重要作用。
实验采用来自雌性豚鼠（270 - 300 g）的离体完整膀胱。膀胱经尿道插管，悬挂于温度为33 - 36℃、含充氧溶液的加热腔室中，并记录膀胱内压。所有药物均添加到浴于膀胱浆膜面的溶液中。
当向静息膀胱中加入α,β-MATP（30 - 3000 nmol/L）或P物质（30 - 300 nmol/L）时，膀胱内压有小幅升高（<2 cmH₂O）。然而，在膀胱暴露于毒蕈碱激动剂槟榔次碱（100 - 300 nmol/L）或烟碱配体洛贝林（10 - 30 μmol/L）所产生的时相性活动存在的情况下，类似浓度或更低浓度的α,β-MATP或P物质会产生更显著的效应：α,β-MATP和P物质（均为100 nmol/L）可使基础压力升高>15 cmH₂O，并增加时相性活动的频率。去除α,β-MATP或P物质后，时相性活动减缓，表明存在抑制机制。
激动剂α,β-MATP和P物质除了对平滑肌有直接作用外，似乎还是产生时相性活动机制的有效调节因子。一个逐渐形成的概念是，负责产生非排尿活动时相性活动的机制是兴奋性和抑制性输入的靶点。调节这种活动可能是产生或改变膀胱感觉的一个因素。不适当或过度的时相性活动可能是导致膀胱过度活动症病理变化的基础，从而为膀胱过度活动症的神经源性和肌源性假说增添了另一种假说，即自主性膀胱假说。
