Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury

被引：90
作者：
Smith, Christopher P. [1 ]
Gangitano, David A. [1 ]
Munoz, Alvaro [1 ]
Salas, Nilson A. [1 ]
Boone, Timothy B. [1 ]
Aoki, K. Roger [2 ]
Francis, Joseph [2 ]
Somogyi, George T. [1 ]
机构：
[1] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA
[2] Allergan Pharmaceut Inc, Irvine, CA 92623 USA
来源：
NEUROCHEMISTRY INTERNATIONAL | 2008年 / 52卷 / 06期
关键词：
botulinum toxin; bladder; nitric oxide; ATP; urothelium; spinal cord injury;
D O I：
10.1016/j.neuint.2007.11.006
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The purpose of this paper was to simultaneously examine changes in urothelial ATP and NO release in normal and spinal cord injured animals as well as in spinal cord injured animals treated with botulinum toxin type A (BoNT-A). Furthermore we correlated changes in transmitter release with functional changes in bladder contraction frequency, and determined the effects of BoNT-A on bladder efferent nerve function. Normal and spinal cord injured rat bladders were injected on day 0 with either vehicle (saline containing bovine serum albumin) or BoNT-A. On day 2, in vitro neurotransmitter release and bladder strip contractility studies as well as in vivo cystometrographic studies were conducted. Resting ATP release was significantly enhanced following spinal cord injury (i.e. 57% increase, p < 0.05) and was unaffected by BoNT-A treatment. SCI increased hypoosmotic evoked urothelial ATP release by 377% (p < 0.05). BoNT-A treatment reduced evoked ATP release in SCI bladders by 83% (p < 0.05). In contrast, hypoosmotic stimulation induced NO release was significantly inhibited following SCI (i.e. 50%, p < 0.05) but recovered in SCI rats treated with BoNT-A (i.e. 195% increase in NO release in SCI-BTX-treated rats compared to SCI controls, p < 0.01). Changes in urothelial transmitter release coincided with a significant decrease in non-voiding bladder contraction frequency (i.e. 71%, p < 0.05) in SCI-BTX rats compared to SCI rats. While no difference was measured between neurally evoked contractile amplitude between SCI and SCI-BTX animals, atropine (1 mu M) inhibited contractile amplitude to a greater extent (i.e. 76%, p < 0.05) in the SCI-BTX group compared to the SCI group. We hypothesize that alterations in the ratio of excitatory (i.e. ATP) and inhibitory (i.e. NO) urothelial transmitters promote bladder hyperactivity in rat bladders following SCI that can be reversed, to a large extent, by treatment with BoNT-A. (C) 2007 Elsevier Ltd. All rights reserved.
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收藏
页码：1068 / 1075
页数：8
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