Differential Effects of Botulinum Neurotoxin A on Bladder Contractile Responses to Activation of Efferent Nerves, Smooth Muscles and Afferent Nerves in Rats

作者：Takahashi Ryosuke; Yunoki Takakazu; Naito Seiji; Yoshimura Naoki^*

来源：Journal of Urology, 2012, 188(5): 1993-1999.

DOI：10.1016/j.juro.2012.07.001

• urinary bladder
• muscle contraction
• botulinum toxins, type A
• calcium channels
• efferent pathways

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 Ca2+ channels, and efferent and afferent nerve terminals in the rat bladder. %26lt;br%26gt;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 Ca2+ channels, and efferent and afferent nerve terminals induced by 70 mM KCl, electrical field stimulation and 1 mu M capsaicin, respectively. %26lt;br%26gt;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. %26lt;br%26gt;Conclusions: The order of inhibitory potency of botulinum neurotoxin A was efferent nerve terminals %26gt;L-type voltage-gated Ca2+ channels %26gt;afferent nerve terminals. Since the inhibitory effects on L-type voltage-gated Ca2+ 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 Ca2+ channels may have an important role in regulating and stabilizing bladder activity.

• 出版日期2012-11