Smith Christopher P, Vemulakonda Vijaya M, Kiss Susanna, Boone Timothy B, Somogyi George T
Scott Department of Urology, Baylor College of Medicine, One Baylor Plaza, Alkek N720, Houston, TX 77030, USA.
Neurochem Int. 2005 Sep;47(4):291-7. doi: 10.1016/j.neuint.2005.04.021.
The effects of mechanoreceptor stimulation and subsequent ATP release in cyclophosphamide evoked chronic bladder inflammation was examined to demonstrate: (1) whether inflammation modulates ATP release from bladder urothelium and (2) whether intravesical botulinum toxin A administration inhibits urothelial ATP release, a measure of sensory nerve activation. ATP release was measured from rat bladders in a Ussing chamber, an apparatus that allows one to separately measure resting and mechanoreceptor evoked (e.g. hypoosmotic stimulation) ATP release from urothelial and serosal sides of the bladder. Cystometry was utilized to correlate changes in ATP release with alterations in the frequency of voiding and non-voiding bladder contractions, in vivo measures of bladder afferent activity. The resting urothelial release of ATP was not significantly affected by either cyclophosphamide or botulinum toxin A treatment. However, evoked ATP release following hypoosmotic stimulation was significantly increased (i.e. 94%) in chronic cyclophosphamide treated bladder urothelium compared to control bladders. In addition, botulinum toxin A treatment significantly reduced hypoosmotic shock induced ATP release in cyclophosphamide treated animals by 69%. Cystometry revealed that cyclophosphamide and botulinum toxin A treatments altered non-voiding (i.e. cyclophosphamide increased, botulinum toxin A decreased) but not voiding contraction frequency suggesting that alterations in urothelial ATP release selectively diminished underlying bladder C-fiber nerve activity. Finally, intravesical instillation of botulinum toxin A did not affect ATP release from the serosal side implying that its effects were confined to the urothelial side of the bladder preparation.
研究了机械感受器刺激及随后的ATP释放对环磷酰胺诱发的慢性膀胱炎症的影响，以证明：（1）炎症是否调节膀胱尿路上皮的ATP释放；（2）膀胱内注射肉毒杆菌毒素A是否抑制尿路上皮ATP释放，这是一种感觉神经激活的指标。在Ussing小室中测量大鼠膀胱的ATP释放，该装置可分别测量膀胱尿路上皮和浆膜侧静息及机械感受器诱发（如低渗刺激）的ATP释放。采用膀胱测压法将ATP释放的变化与排尿和非排尿膀胱收缩频率的改变相关联，排尿和非排尿膀胱收缩频率是膀胱传入活动的体内测量指标。环磷酰胺或肉毒杆菌毒素A处理均未显著影响ATP的静息尿路上皮释放。然而，与对照膀胱相比，慢性环磷酰胺处理的膀胱尿路上皮在低渗刺激后诱发的ATP释放显著增加（即增加94%）。此外，肉毒杆菌毒素A处理使环磷酰胺处理动物中低渗休克诱导的ATP释放显著降低69%。膀胱测压显示，环磷酰胺和肉毒杆菌毒素A处理改变了非排尿（即环磷酰胺增加，肉毒杆菌毒素A减少）但未改变排尿收缩频率，提示尿路上皮ATP释放的改变选择性地降低了膀胱C纤维神经的基础活动。最后，膀胱内灌注肉毒杆菌毒素A不影响浆膜侧的ATP释放，这意味着其作用局限于膀胱标本的尿路上皮侧。
