title: Differential effects of botulinum neurotoxin A on bladder contractile responses to activation of efferent nerves, smooth muscles and afferent nerves in rats.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Takakazu
authors.initials: T
authors.lastname: Yunoki
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D004525:Efferent Pathways / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D009465:Neuromuscular Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A