Lack of effectiveness of botulinum neurotoxin A on isolated detrusor strips and whole bladders from mice and guinea-pigs in vitro.
OBJECTIVE
To differentiate between the effects of parasympathetic and sensorimotor stimulation of isolated mouse and guinea-pig bladders in vitro by measuring the pressure increases to electrical field stimulation (EFS) and then comparing the effects of botulinum neurotoxin A (BoNT-A) applied either to the lumen or to the external bathing medium.


METHODS
Isolated mouse and guinea-pig bladders and detrusor strips were exposed to EFS in vitro before and after the addition of BoNT-A. The rationale of this method was that BoNT-A applied to the outside of the bladder would first affect the parasympathetic nerves before diffusing inwards to affect the sensorimotor innervation. BoNT-A applied intravesically would first reach the sensorimotor nerves and only later the parasympathetic nerves. Initial experiments on strips of detrusor were conducted to establish the correct dosage and application time of BoNT-A.


RESULTS
Contrary to our expectations, BoNT-A application failed to produce any significant effects on either the detrusor strips or whole bladders.


CONCLUSIONS
Our experimental design failed to show any effect of BoNT-A on the contractility of detrusor muscle strips or whole bladders from mice and guinea-pigs. The reason for this is unclear, but may be related to tissue spending inadequate time incubated with BoNT-A under physiological conditions.
Howles
Sarah
S
Department of Urology, Churchill Hospital, University of Oxford, Oxford, UK. sarah.bounds@doctors.org.uk
Curry
Jonathan
J
McKay
Ian
I
Reynard
John
J
Brading
Alison F
AF
Apostolidis
Apostolos
A
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009465:Neuromuscular Agents / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000502:physiology
D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A