肉毒毒素 A 对大鼠传出神经、平滑肌和传入神经激活引起的膀胱收缩反应的差异作用。

Differential effects of botulinum neurotoxin A on bladder contractile responses to activation of efferent nerves, smooth muscles and afferent nerves in rats.

机构信息

Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.

出版信息

J Urol. 2012 Nov;188(5):1993-9. doi: 10.1016/j.juro.2012.07.001. Epub 2012 Sep 20.

DOI:10.1016/j.juro.2012.07.001

PMID:22999538

Abstract

PURPOSE

To determine the mechanisms of botulinum neurotoxin A (Metabiologics, Madison, Wisconsin) induced inhibition of bladder activity we examined the effect of botulinum neurotoxin A on detrusor contractile responses to the activation of L-type voltage-gated Ca(2+) channels, and efferent and afferent nerve terminals in the rat bladder.

MATERIALS AND METHODS

Rat bladder strips were incubated for 3 hours with different concentrations of botulinum neurotoxin A (0.3 to 100 nM). We examined the effect of botulinum neurotoxin A on detrusor contractility in response to activation of L-type voltage-gated Ca(2+) channels, and efferent and afferent nerve terminals induced by 70 mM KCl, electrical field stimulation and 1 μM capsaicin, respectively.

RESULTS

Botulinum neurotoxin A inhibited electrical field stimulation induced contractions at a concentration of 10 nM or higher. The maximal inhibition at 100 nM was 70% compared to that of control strips. KCl induced contractions, which were sensitive to nifedipine, were significantly inhibited by incubation with botulinum neurotoxin A at a concentration of 3 nM or higher. Maximal inhibition at 100 nM was 30% compared to that of control strips. Capsaicin induced contractions were not inhibited by 3-hour incubation but they were significantly inhibited by overnight incubation with 100 nM botulinum neurotoxin A (30% compared to control strips). Carbachol induced contractions were not altered by incubation with botulinum neurotoxin A.

CONCLUSIONS

The order of inhibitory potency of botulinum neurotoxin A was efferent nerve terminals >L-type voltage-gated Ca(2+) channels >afferent nerve terminals. Since the inhibitory effects on L-type voltage-gated Ca(2+) channels and efferent nerve terminals were observed at similar botulinum neurotoxin A concentrations, the inhibitory effect of botulinum neurotoxin A on L-type voltage-gated Ca(2+) channels may have an important role in regulating and stabilizing bladder activity.

摘要

目的

为了确定肉毒杆菌神经毒素 A（麦迪逊威斯康星州的 Metabiologics）抑制膀胱活动的机制，我们研究了肉毒杆菌神经毒素 A 对大鼠膀胱中 L 型电压门控 Ca(2+) 通道激活、传出和传入神经末梢引起的逼尿肌收缩反应的影响。

材料和方法

将大鼠膀胱条在不同浓度的肉毒杆菌神经毒素 A（0.3 至 100 nM）中孵育 3 小时。我们研究了肉毒杆菌神经毒素 A 对 L 型电压门控 Ca(2+) 通道激活、70 mM KCl、电刺激和 1 μM 辣椒素诱导的逼尿肌收缩的影响。

结果

肉毒杆菌神经毒素 A 在浓度为 10 nM 或更高时抑制电刺激引起的收缩。在 100 nM 时，与对照条带相比，最大抑制率为 70%。对硝苯地平敏感的 KCl 诱导收缩在浓度为 3 nM 或更高时被肉毒杆菌神经毒素 A 孵育显著抑制。在 100 nM 时，与对照条带相比，最大抑制率为 30%。3 小时孵育不能抑制辣椒素诱导的收缩，但 100 nM 肉毒杆菌神经毒素 A 过夜孵育可显著抑制（与对照条带相比，抑制率为 30%）。肉毒杆菌神经毒素 A 孵育不改变乙酰胆碱诱导的收缩。

结论

肉毒杆菌神经毒素 A 的抑制效力顺序为传出神经末梢> L 型电压门控 Ca(2+) 通道>传入神经末梢。由于在相似的肉毒杆菌神经毒素 A 浓度下观察到对 L 型电压门控 Ca(2+) 通道和传出神经末梢的抑制作用，肉毒杆菌神经毒素 A 对 L 型电压门控 Ca(2+) 通道的抑制作用可能在调节和稳定膀胱活动中起重要作用。