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Effect of botulinum toxin A on urothelial‐release of ATP and expression of SNARE targets within the urothelium
Author(s) -
HannaMitchell Ann T.,
WolfJohnston Amanda S.,
Barrick Stacey R.,
Kanai Anthony J.,
Chancellor Michael B.,
de Groat William C.,
Birder Lori A.
Publication year - 2015
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.22508
Subject(s) - urothelium , urothelial cell , botulinum toxin , urinary bladder , intracellular , overactive bladder , medicine , pharmacology , biology , microbiology and biotechnology , pathology , anesthesia , alternative medicine
Aims 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. Methods 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. Results 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%). Conclusions 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. 34:79–84, 2015 . © 2013 Wiley Periodicals, Inc.