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

Ryosuke Takahashi, Takakazu Yunoki, Seiji Naito, Naoki Yoshimura

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish
Pages (from-to)1993-1999
Number of pages7
JournalJournal of Urology
Volume188
Issue number5
DOIs
Publication statusPublished - Nov 1 2012

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Type A Botulinum Toxins
Neurotoxins
Smooth Muscle
Urinary Bladder
Capsaicin
Electric Stimulation
Carbachol
Nifedipine

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

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 journalArticle

Takahashi, Ryosuke ; Yunoki, Takakazu ; Naito, Seiji ; Yoshimura, Naoki. / Differential effects of botulinum neurotoxin a on bladder contractile responses to activation of efferent nerves, smooth muscles and afferent nerves in rats. In: Journal of Urology. 2012 ; Vol. 188, No. 5. pp. 1993-1999.
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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.",
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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

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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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