Salas Nilson A, Somogyi George T, Gangitano David A, Boone Timothy B, Smith Christopher P
NeuroUrology Laboratory, Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA.
Neurochem Int. 2007 Jan;50(2):345-50. doi: 10.1016/j.neuint.2006.09.002. Epub 2006 Oct 25.
Neurally intact (NI) rats and chronic spinal cord injured (SCI) rats were studied to determine how activation of mechanosensory or cholinergic receptors in the bladder urothelium evokes ATP release from afferent terminals in the bladder as well as in the spinal cord. Spinal cord transection was performed at the T(9)-T(10) level 2-3 weeks prior to the experiment and a microdialysis fiber was inserted in the L(6)-S(1) lumbosacral spinal cord one day before the experiments. Mechanically evoked (i.e. 10 cm/W bladder pressure) ATP release into the bladder lumen was approximately 6.5-fold higher in SCI compared to NI rats (p<0.05). Intravesical carbachol (CCh) induced a significantly greater release of ATP in the bladder from SCI as compared to NI rats (3424.32+/-1255.57 pmol/ml versus 613.74+/-470.44 pmol/ml, respectively, p<0.05). However, ATP release in NI or SCI rats to intravesical CCh was not affected by the muscarinic antagonist atropine (Atr). Spinal release of ATP to bladder stimulation with 10 cm/W pressure was five-fold higher in SCI compared to NI rats (p<0.05). CCh also induced a significantly greater release of spinal ATP in SCI rats compared to controls (4.3+/-0.9 pmol versus 0.90+/-0.15 pmol, p<0.05). Surprisingly, the percent inhibitory effect of Atr on CCh-induced ATP release was less pronounced in SCI as compared to NI rats (49% versus 89%, respectively). SCI induces a dramatic increase in intravesical pressure and cholinergic receptor evoked bladder and spinal ATP release. Muscarinic receptors do not mediate intravesical CCh-induced ATP release into the bladder lumen in NI or SCI rats. In NI rats sensory muscarinic receptors are the predominant mechanism by which CCh induces ATP release from primary afferents within the lumbosacral spinal cord. Following SCI, however, nicotinic or purinergic receptor mechanisms become active, as evidenced by the fact that Atr was only partially effective in inhibiting CCh-induced spinal ATP release.
对神经完好（NI）大鼠和慢性脊髓损伤（SCI）大鼠进行了研究，以确定膀胱尿路上皮中机械感觉受体或胆碱能受体的激活如何引发膀胱以及脊髓中传入神经末梢释放ATP。在实验前2 - 3周于T(9)-T(10)水平进行脊髓横断，并在实验前一天将微透析纤维插入L(6)-S(1)腰骶脊髓。与NI大鼠相比，SCI大鼠中机械诱发（即10 cm/W膀胱压力）的ATP释放到膀胱腔中的量约高6.5倍（p<0.05）。与NI大鼠相比，膀胱内注射卡巴胆碱（CCh）在SCI大鼠膀胱中诱导的ATP释放显著增加（分别为3424.32±1255.57 pmol/ml和613.74±470.44 pmol/ml，p<0.05）。然而，NI或SCI大鼠中膀胱内CCh诱导的ATP释放不受毒蕈碱拮抗剂阿托品（Atr）的影响。与NI大鼠相比，SCI大鼠中用10 cm/W压力刺激膀胱时脊髓释放的ATP高5倍（p<0.05）。与对照组相比，CCh在SCI大鼠中也诱导脊髓ATP释放显著增加（4.3±0.9 pmol对0.90±0.15 pmol，p<0.05）。令人惊讶的是，与NI大鼠相比，Atr对CCh诱导的ATP释放的抑制作用百分比在SCI大鼠中不太明显（分别为49%对89%）。SCI导致膀胱内压力显著增加以及胆碱能受体诱发膀胱和脊髓ATP释放。毒蕈碱受体在NI或SCI大鼠中不介导膀胱内CCh诱导的ATP释放到膀胱腔中。在NI大鼠中，感觉毒蕈碱受体是CCh诱导腰骶脊髓内初级传入神经释放ATP的主要机制。然而，SCI后，烟碱或嘌呤能受体机制变得活跃，这一事实证明Atr在抑制CCh诱导的脊髓ATP释放方面仅部分有效。
