Gillespie J I
The Urophysiology Research Group, School of Surgical and Reproductive Sciences, The Medical School, The University, Newcastle upon Tyne, UK.
BJU Int. 2004 Feb;93(3):401-9. doi: 10.1111/j.1464-410x.2003.04626.x.
To investigate the actions of noradrenaline and the specific alpha-adrenergic agonists cirazoline (alpha1) and UK14304 (alpha2), and beta-receptor agonists formoterol (beta2) and BRL37344 (beta3) on the phasic activity induced by muscarinic stimulation on the isolated guinea pig bladder, as the physiological significance of this activity is unknown but it may underlie non-micturition contractions (NMCs, which can be inhibited by sympathetic nerve stimulation) and the generation of bladder sensations.
All experiments were conducted using whole isolated bladders from female guinea pigs (270-300 g). Bladders were cannulated via the urethra and suspended in a heated chamber containing oxygenated Tyrode's solution at 33-35 degrees C and the intravesical pressure recorded. All drugs were added to the solution bathing the abluminal surface.
Exposure to noradrenaline reduced the amplitude and frequency of the phasic activity. When noradrenaline was washed off there was a transient increase in frequency. There was marked desensitization with repeated applications of noradrenaline. Applying the specific beta3-agonist BRL37344 reduced the amplitude of the phasic activity while formoterol, a specific beta2-agonist, had no effect. Cirazoline, a specific alpha1-agonist, reduced the amplitude of the responses and significantly reduced the frequency of the phasic activity. UK14304, a specific alpha2-agonist, had no effect. Stimulation of the hypogastric nerve to the guinea pig bladder generates contractions. Prolonged nerve stimulation at low frequency (6.5 Hz) generated phasic rises in intravesical pressure which were inhibited by noradrenaline. Using short (5 s) periods of stimulation noradrenaline inhibited nerve-mediated contractions at all frequencies but was more effective at <10 Hz.
These experiments show that sympathomimetic stimulation in the isolated whole bladder results primarily in an inhibition of phasic activity, but also a stimulation. Two receptor subtypes appear to be involved in the inhibition, alpha1 and beta3, suggesting that there may be many sites of action. These results are discussed in terms of the possible physiological significance of phasic activity and the potential importance of its inhibition, in the context of the causes of pathological changes in the bladder, particularly those associated with bladder overactivity, and the pharmacological approach to the alleviation of clinical symptoms.
研究去甲肾上腺素以及特异性α-肾上腺素能激动剂西拉唑啉（α1）和 UK14304（α2），还有β-受体激动剂福莫特罗（β2）和 BRL37344（β3）对毒蕈碱刺激诱导的离体豚鼠膀胱相性活动的作用，因为这种活动的生理意义尚不清楚，但它可能是非排尿收缩（NMCs，可被交感神经刺激抑制）和膀胱感觉产生的基础。
所有实验均使用来自雌性豚鼠（270 - 300 克）的完整离体膀胱进行。膀胱通过尿道插管，并悬挂在一个加热的腔室中，该腔室含有 33 - 35 摄氏度的含氧台氏液，并记录膀胱内压。所有药物均添加到浸泡膀胱浆膜面的溶液中。
暴露于去甲肾上腺素会降低相性活动的幅度和频率。当洗去去甲肾上腺素后，频率会有短暂增加。重复应用去甲肾上腺素会出现明显的脱敏现象。应用特异性β3 - 激动剂 BRL37344 会降低相性活动的幅度，而特异性β2 - 激动剂福莫特罗则无作用。特异性α1 - 激动剂西拉唑啉会降低反应幅度，并显著降低相性活动的频率。特异性α2 - 激动剂 UK14304 则无作用。刺激豚鼠膀胱的腹下神经会产生收缩。在低频（6.5 赫兹）下长时间神经刺激会使膀胱内压出现相性升高，而去甲肾上腺素可抑制这种升高。使用短时间（5 秒）刺激时，去甲肾上腺素在所有频率下均能抑制神经介导的收缩，但在频率小于 10 赫兹时更有效。
这些实验表明，在离体完整膀胱中，拟交感神经刺激主要导致相性活动受到抑制，但也有刺激作用。两种受体亚型似乎参与了这种抑制作用，即α1 和β3，这表明可能存在多个作用位点。结合相性活动可能的生理意义及其抑制的潜在重要性，在膀胱病理变化的原因，特别是与膀胱过度活动相关的原因，以及缓解临床症状的药理学方法的背景下，对这些结果进行了讨论。
