TY - JOUR
T1 - Differential effects of botulinum neurotoxin a on bladder contractile responses to activation of efferent nerves, smooth muscles and afferent nerves in rats
AU - Takahashi, Ryosuke
AU - Yunoki, Takakazu
AU - Naito, Seiji
AU - Yoshimura, Naoki
N1 - Funding Information:
Supported by National Institutes of Health Grants ( DK057267 and DK088836 ), Department of Defense Grant SC100134 and Paralyzed Veterans of America Grant 2793 .
PY - 2012/11
Y1 - 2012/11
N2 - 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. 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 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 Ca2+ channels >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.
AB - 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. 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 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 Ca2+ channels >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.
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U2 - 10.1016/j.juro.2012.07.001
DO - 10.1016/j.juro.2012.07.001
M3 - Article
C2 - 22999538
AN - SCOPUS:84867395849
VL - 188
SP - 1993
EP - 1999
JO - Investigative Urology
JF - Investigative Urology
SN - 0022-5347
IS - 5
ER -