title: Targets for botulinum toxin in the lower urinary tract.
abstract: BACKGROUND
  Botulinum toxin type A (BoNT/A), one of the seven subtypes of Botulinum toxin, is commercially available naked or complexed to other proteins. Onabotulinum toxin type A is the most extensively studied BoNT/A brand. Dose equivalence studies between the different brands have never been carried out. BoNT/A is internalized by nerve fibers after binding synaptic vesicle proteins, and the final target of action is synaptosome-associated protein 25 kDa (SNAP-25), a membrane protein essential for synaptic vesicle fusion with the neuronal membrane.
  
  
  METHODS
  The current literature about botulinum toxin mechanisms was reviewed to provide an up to date knowledge about the topic.
  
  
  RESULTS
  Immunoreactivity to cleaved SNAP-25, the end product of BoNT/A activity, has been identified in parasympathetic (pre- and postganglionic), sympathetic, and afferent fibers. A consistent decrease in the release of acetylcholine from parasympathetic, norepinephrine from sympathetic, and glutamate and neuropeptides from sensory neurons follows BoNT/A administration. Immunoreactivity to cleaved SNAP-25 was not identified in the urothelium or in myofibroblasts. Nevertheless, a decreased release of ATP and neurotrophins from the urothelial cells has been consistently observed after BoNT/A. The toxin does not cause apoptosis in the bladder. However, injection in rat and dog prostates was shown to induce apoptosis in acinar and stromal cells.
  
  
  CONCLUSIONS
  There is now robust information to support that the mechanism of action of BoNT/A in the bladder involves neurotransmitter release from nerve fibers and urothelial cells. Which neurotransmitter is more relevant is, however, unclear. Likewise, the long duration of effect, the importance of the volume of vehicle injected and the selection of specific injection sites, like the trigone, needs further evaluation.
authors.affiliation: Department of Urology and IBMC, Hospital de São João and Faculty of Medicine of Porto, Porto, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Cruz
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D006801:Humans; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009465:Neuromuscular Agents / Q000627:therapeutic use*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D064804:Urological Agents / Q000627:therapeutic use*; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
chemical_list: D009465:Neuromuscular Agents; D050825:Synaptosomal-Associated Protein 25; D064804:Urological Agents; D019274:Botulinum Toxins, Type A
keywords: SNAP-25; botulinum toxin type A; overactive bladder