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 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1993-1999 |
| Number of pages | 7 |
| Journal | Journal of Urology |
| Volume | 188 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Nov 1 2012 |
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All Science Journal Classification (ASJC) codes
- Urology
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Differential effects of botulinum neurotoxin a on bladder contractile responses to activation of efferent nerves, smooth muscles and afferent nerves in rats. / Takahashi, Ryosuke; Yunoki, Takakazu; Naito, Seiji; Yoshimura, Naoki.
In: Journal of Urology, Vol. 188, No. 5, 01.11.2012, p. 1993-1999.Research output: Contribution to journal › Article
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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
PY - 2012/11/1
Y1 - 2012/11/1
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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UR - http://www.scopus.com/inward/citedby.url?scp=84867395849&partnerID=8YFLogxK
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 - Journal of Urology
JF - Journal of Urology
SN - 0022-5347
IS - 5
ER -