Karl-Erik Andersson led the peer-review process as the Associate Editor responsible for the paper.
Original Basic Science Article
Effect of botulinum toxin A on urothelial-release of ATP and expression of SNARE targets within the urothelium
Article first published online: 26 OCT 2013
© 2013 Wiley Periodicals, Inc.
Neurourology and Urodynamics
How to Cite
Hanna-Mitchell, A. T., Wolf-Johnston, A. S., Barrick, S. R., Kanai, A. J., Chancellor, M. B., de Groat, W. C. and Birder, L. A. (2013), Effect of botulinum toxin A on urothelial-release of ATP and expression of SNARE targets within the urothelium. Neurourol. Urodyn.. doi: 10.1002/nau.22508
- Article first published online: 26 OCT 2013
- Manuscript Accepted: 13 SEP 2013
- Manuscript Received: 16 MAY 2013
- NIH. Grant Numbers: R37 DK54824, R01 DK57284, K01 DK080184, R01 DK083323
- bladder mucosa;
Botulinum neurotoxin serotype A (BoNT/A) has emerged as an effective treatment of urinary bladder overactivity. Intravesical lipotoxin (BoNT/A delivery using liposomes), which may target the urothelium, is effective in blocking acetic acid induced hyperactivity in animals. The objective of this study was to assess the possible site of toxin action within the urothelium.
We examined expression of the toxin receptor (SV2) and its cleavage targets (SNAP-25 and SNAP-23) within urothelium as well as effects of the toxin on mechanically evoked release of ATP from cultured rat urothelial cells. ATP release was measured using the luciferin-luciferase assay; we examined expression of SNAP-23 and -25 in urothelial cells and mucosa of rat and human bladders.
BoNT/A (1.5 U; 1–3 hr) blocked hypotonic evoked release of urothelial ATP, without affecting morphology. The expression of protein targets for BoNT/A binding (SV2) was detected in human and rat bladder mucosa and catalytic action (SNAP-23, -25) in urothelial cells and mucosa (differed in intensity) from rat and human bladder. Incubation of cultured (rat) urothelial cells with BoNT/A decreased expression levels of both SNAP-23 (44%) and SNAP-25 (80%).
Our findings reveal that the bladder urothelium expresses the intracellular targets and the binding protein for cellular uptake of BoNT/A; and that the toxin is able to suppress the levels of these targets as well as hypotonic-evoked ATP release. These data raise the possibility that intravesical treatment with BoNT/A suppresses bladder reflex and sensory mechanisms by affecting a number of urothelial functions including release of transmitters. Neurourol. Urodynam. © 2013 Wiley Periodicals, Inc.